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Administration of t-PA (Activase) in

Administration of t-PA (Activase) in. ACUTE ISCHEMIC STROKE. August 2007. Information was produced and/or compiled by the Alberta Provincial Stroke Strategy and written permission is required prior to reprinting any of the material located within this document. 09/07:09/08[R].

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Administration of t-PA (Activase) in

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  1. Administration of t-PA (Activase) in ACUTE ISCHEMIC STROKE August 2007 Information was produced and/or compiled by the Alberta Provincial Stroke Strategy and written permission is required prior to reprinting any of the material located within this document. 09/07:09/08[R]

  2. Administration of tPA (Activase) in Acute Ischemic Stroke Learning Objectives: Upon completion of this session, participants will be able to: • Describe the action of tPA in relation to acute ischemic stroke • Identify criteria necessary for the administration of tPA in acute ischemic stroke • Explain recommended preparation, administration, assessment and on-going care of tPA infusion • Identify possible adverse effects of tPA administration

  3. Thrombolysis in Acute Stroke Rationale: • Limit size of infarct by dissolving clot & restoring blood flow to ischemic brain • Neuronal death & infarction evolve in a time dependent manner • Prompt treatment with a thrombolytic agent may promote reperfusion & improve functional outcomes

  4. Thrombolytic Agents 1st generation: • Streptokinase • Urokinase • Anistreplase 2nd generation: • Pro-urokinase • Alteplase (recombinant tissue plasminogen activator [rtPA])

  5. Thrombolytic Agents 3rd generation: • Reteplase • Lanoteplase • Tenecteplase (TNK) • Desmoteplase (in phase 3 trials) Ancrod (defibrinogenating enzyme)

  6. rt-PA (Activase): Clinical Trial NINDS Study (1995) • Double-blind, placebo-cont., randomized • 624 patients • IV tPA (0.9 mg/kg) given <3 hrs stroke onset 10% bolus then 90% infusion over 1 h • Favorable outcomes • 31%-51% rtPA treated group • 20%-38% placebo group

  7. rt-PA (Activase): Clinical Trial NINDS Study (1995) cont: • 32% more tPA pts had minimal or no disability • Measured by Barthel Index • Symptomatic Intracranial hemorrhage by 36 h: • 6.4% tPA • 0.6% placebo (P<.001) • Mortality by 3 months: • 17% tPA, • 21% placebo

  8. rt-PA (Activase) in Acute Ischemic Stroke Thrombolytic (clot buster) given IV for treatment for acute ischemic stroke: • Approved in US in 1996 • Approval in Canada in 1999 • CASES - 2002 (Canadian Study) • 1135 patients treated • Hemorrhage rate - 4.6% • Anaphylactic/angioedema reaction - 1.3% • Favorable outcomes at 3 months & 12 months

  9. NINDS tPA Stroke Study: Time to Treatment and Odds Ratio of Favorable Outcome 8 TIME IS BRAIN !!! 7 6 Odds Ratio Favorable Outcome 5 4 3 2 Benefit for rt-PA 1 m No Benefit for rt-PA 0 60 70 80 90 100 110 120 130 140 150 160 170 180 Minutes Stroke Onset To Start of Treatment

  10. Diminishing Returns over Time Favorable Outcome (mRS 0-1, BI 95-100, NIHH 0-1) at Day 90 Adjusted odds ratio with 95% confidence interval by stroke onset to treatment time (OTT) ITT population (N=2776) Pooled Analysis NINDS tPA, ATLANTIS, ECASS-I, ECASS-II Courtesy Brott T et al

  11. BRAIN ATTACKTIME IS BRAIN! • Get drug in fast! • 1.9 million neurons are destroyed each minute treatment is delayed • Goal - door to drug < 30 min

  12. Pathophysiology and tPA • Thrombus is formed during ischemic stroke. • Alteplase binds to fibrin in a thrombus: • converts plasminogen to plasmin • initiates local fibrinolysis with minimal systemic effects. • Cleared rapidly from circulating plasma by liver. • >50% cleared within 5 min after infusion • 80% cleared within 10 min

  13. Pathophysiology and tPA • Reperfusion - thrombolytic (intravenous tPA)

  14. Indications for tPA therapy: • Patients presenting within 3hrsof an acute ischemic stroke who meet the inclusion criteria for thrombolysis • To be given < 3 hours after stroke symptom onset • May be given < 6hrs only under care of Stroke Neurologist

  15. Onset Time • Onset Time = Time when patient was last seen well • Requires detective skills

  16. Inclusion Criteria • Acute ischemic stroke presenting within 3 hours of onset of symptoms. • No hemorrhage on CT • No evidence of massive infarction or edema involving >1/3 MCA territory • No midline shift (mass effect) • No evidence tumor, aneurysm or AVM

  17. Exclusion Criteria: • Decreased level of consciousness • Symptom onset >3 hrs • SAH, aneurysm, AVM, ICH, mass effect, tumor on CT, or any major hypodensity representing well-evolved infarction • Stroke or serious head injury within 3 months

  18. Exclusion Criteria(Continued): • Previous CNS bleeding • Hx of GI/GU hemorrhage <21 days • Major trauma/surgery <14 days • Hematological abnormality or coagulopathy, INR >1.7 • Arterial puncture at a non-compressible site in the last 7 days

  19. Exclusion Criteria (Continued): • HTN (BP >185/110 not responding to antihypertensive tx) • Pericarditis <3 months • Serious underlying medical illness where the benefit of tPA is doubtful and the risks high

  20. Prior to Infusion of tPA: • EMS / Bypass, ER protocols • Early arrival to ER (best if within 2 hours) • Rapid Assessment - ABC’s, LOC • Ensure Bloodwork is drawn: • CBC (Plts), Lytes, BUN, Glucose, Troponin, INR, PTT, • Determine eligibility for tPA based on the inclusion/exclusion criteria. • TIME of ONSET is CRITICAL! • CT ASAP

  21. Prior to Infusion of tPA: • IV Access: start 2 IV’s • #1: used only for tPA • Saline Lock post infusion, and use for blood drawing only • #2: ‘life line’ • for IV drug access/fluid administration • Blood pressure management • Maintain SBP < 185 mmHg &/or DBP < 110 mmHg • Patient / family education

  22. Preparing tPA - 100mg Vial • Package Contains: • 100 mg vial of Activase • 100 ml vial of sterile H20 • A double-sided sterile transfer device • Insert one end of transfer device into vial containing diluent TIME IS BRAIN!

  23. Preparing tPA (continued) • Holding Activase vial upside down, insert other end of transfer device into center of the stopper • Invert vials

  24. Preparing tPA (continued) • DO NOT SHAKE THE VIAL AS IT WILL DENATURE THE PROTEIN STRANDS • Allow vials to sit undisturbed till foam subsides (takes only seconds) • Remove transfer device once the drug is reconstituted.

  25. Preparing tPA (continued) • Infusion Chart: Look up patient’s weight to determine bolus and infusion amounts • Spike reconstituted vial of tPA with infusion tubing, and prime line • Set infusion pump rate and volume limit for BOLUS as specified for patient’s weight • 10% of total dose given over 60 seconds • Once bolus infused, set infusion pump rate and volume limit for continuous infusion as specified for patient’s weight • 0.9 mg/kg given over 60 minutes tPA Must be given with an INFUSION PUMP!!

  26. Precautions!! • Do not mix tPA with any other medications. • Do not use IV tubing with infusion filters. • All patients must be on a cardiac monitor • When infusion is complete, saline lock IV and flush with N/S • tPA must be used within 8 hours of mixing when stored at room temperature or within 24 hours if refrigerated

  27. Assessment during tPA - VS • Assess NVS • q15min x 2 hrs then q30 min x 6 hrs, q1hr x 16 hrs and q4 hrs x 48 hrs • Assess NIHSS • Immediately after tPA bolus, repeat at 30min, 60min, 3hr, 6hr and 24hr post tPA initiation If evidence of bleeding, neurological deterioration (change of 2+ points on NIHSS), new headache or nausea: - notify physician - arrange CT scan

  28. Assessment during tPA - VS • Assess BP and Pulse • q15min x 2 hrs then q30 min x 6 hrs, q1hr x 16 hrs and q4 hrs x 48 hrs • If SBP >180mmHg &/or DBP >105mmHg notify physician and consider the following treatment: • Labetalol 10-20 mg IV over 1-2 min, repeat q10-20 min (max 150 mg) • If Labetalol ineffective, alternates include: • Hydralazine 10 mg IV push over 1-2min, q10-20 min • Enalaprilat 1.25 mg IV push over 1 min, q6h • Sodium nitroprusside 0.5-10 ug/kg/min

  29. Nursing Care during tPA • Avoid taking BP in arm with IV’s or venipunctures. • BP should be taken manually • an NIBP will cause petechiae • Avoid unnecessary handling of the patient. • Bed rest x 12 hours then reassess

  30. Nursing Care during tPA • No unnecessary venous or arterial punctures • Blood is drawn from IV saline lock if possible • Avoid invasive procedures • NG tubes, suction, or urinary catheterization • Apply pressure dressing to potential sources of bleeding • Assess all secretions and excretions for blood

  31. APSS Recommended tPA Protocol Diet • NPO pending swallow screen • Complete swallow screen prior to any oral intake • If fails, keep NPO then reassess Glucose • Monitor capillary glucose as follows: • If diabetic or lab glucose >10 mmol/L • q4h x 24hr then reassess • If non-diabetic or lab glucose < 10 mmol/L • qid x 48 hr then reassess If glucose elevated: recommend insulin sliding scale (sc or IV)

  32. APSS Recommended tPA Protocol Antiplatelet/Anticoagulant Therapy • No ASA, Clopidogrel, Aggrenox, Ticlopidine or other antiplatelet agents for 24 hours from start of tPA • No heparin, heparinoid or warfarin for 24 hours from start of tPA CT or MRI must be completed and reviewed by physician to exclude intracranial hemorrhage prior to above therapy

  33. APSS Recommended tPA Protocol DVT Prophylaxis • Assess patient daily for deep vein thrombosis • Intermittent pneumonic compression stockings while on bed rest, then reassess • After 24h, if CT/MR is negative for hemorrhage, consider the following when patient remains on bed rest due to significant lower limb hemiparesis/plegia: • Unfractionated heparin sc 5000u q12 h OR • Enoxaparin 40mg sc q24h

  34. APSS Recommended tPA Protocol Bladder Management • If possible, catheterize before tPA admin • DO NOT DELAY tPA for this • Avoid catheterization 5-7 hrs post tPA infusion • If unable to void - bladder scanner and in/out catheterization q4-6hrs • If voiding - residuals daily until < 100 ml

  35. Adverse Effects of tPA Bleeding • Superficial: due to lysis of fibrin in the hemostatic plug • observe potential bleeding sites: venous & arterial puncture, lacerations, etc. • Internal: • GI tract, GU tract, Respiratory, Retroperitoneal or Intracerebral ACTIONS: If clinically significant bleeding or deterioration of Neuro status: STOPtPA and notify physician.

  36. Adverse Effects of tPA Angioedema • Assess patient for signs of Angioedema of the tongue: • Swelling of tongue/lips • notify Physician immediately if swelling seen • 1.3% of population • Assess at 30, 45, 60, 75 minutes after tPA bolus. Once the tPA infusion has finished the risk of angioedema falls off • Patients on ACEi are at higher risk of angioedema

  37. Adverse Effects of tPA Nausea & Vomiting • 25% of patients Allergy/Anaphylaxis • <0.02% of patients • Observe for skin eruptions, airway tightening • Unexplained hypotension may occur as an immune reaction

  38. Patient/Family Education Educate patients and family regarding: • Purpose of therapy • Potential side effects

  39. Follow-Up: • Repeat CT scan or MRI scan at 12-36 hrs (approx 24 hrs) post tPA • Daily Neuro assessments after first 24 hours

  40. Successful Outcome“On the table responders” “Lazarus effect” 1 in 4-5 tPA patients versus 1 in 30 placebo patients NIHSS

  41. Successful Outcome of IV tPA therapy: • Thrombolysis of arterial occlusion • Reperfusion of viable tissue • Improvement in pt functioning/outcome • Improvement can be delayed • only uncommonly occurs in the first 24h • Rehabilitation and reintegration

  42. THROMBOLYTICS: Beyond the 3 hr Time Window

  43. Thrombolytics: Beyond the 3 hr Time Window Learning Objective: Upon completion of this session, participants will be able to: • Describe circumstances in which tPA may be infused beyond the 3 hour time window

  44. Thrombolytics: Beyond the 3 hr Time Window • Meta-analysis of 6 randomized controlled trials of IV tPA • The sooner the tPA the greater the benefit • Best outcome if treated <2 hours • Some benefit out to 5 hours • Imaging might assist to select patients who would benefit with treatment beyond 3 hours: • MRI: Diffusion / Perfusion weighted imaging • CT based perfusion imaging • Intra-arterial thrombolytic administration is being studied

  45. Thrombolytics: Beyond the 3 hr Time Window Imaging • Magnetic Resonance Imaging (MRI) • Diffusion weighted imaging (DWI) • Evolving brain edema results in disturbed diffusion • Damaged brain tissue • Early detection of ischemic brain • Perfusion weighted imaging (PWI) • Obtained following injection of a contrast agent • Identifies areas of decreased perfusion

  46. MRI-Mismatch Concept DWI-Core of Infarct MRA Vessel Occlusion Tissue at Risk Impaired Perfusion PWI T2* Rule out ICH Jansen ea, Lancet 1999

  47. Intra-Arterial Thrombolysis: Beyond the 3 hr Time Window • Infuse thrombolytic agent at site of occlusion through microcatheter • Remains experimental • Not approved in Canada or US • May show some benefit in treatment of carefully selected patients • Hemorrhage remains substantial concern

  48. Intra-Arterial Thrombolysis: Beyond the 3 hr Time Window • PROACT II study - Prolyse in Acute Cerebral Thrombolism • Prospective, randomized, placebo-controlled, phase III • Effectiveness of IA thrombolysis with Prourokinase • Patients with ischemic stroke secondary to occlusion of MCA • < 6 hours from stroke symptom onset Results: • Rankin 0-2 at 90 day: 40% in treatment group (121 patients) 25% in control group (59 patients) • Recanalization of MCA: 66% treatment, 18% control • SICH within 24 hours: 10% treatment, 2% control No difference in overall death rate Not approved: Prourokinase not available for clinical use

  49. Intra-Arterial Thrombolysis: Beyond the 3 hr Time Window • Results of PROACT II extrapolated to tPA and urokinase • IA promoted due to: • General consensus and case data • High concentration of drug delivered into thrombus • Clinicians observe higher recanalization rates with IA than IV tPA (uncontrolled) • Clinical benefit may be offset by delay to initiate IA treatment

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