Stroke & Cerebrovascular Center

Services - Stroke Prevention & Treatment

Acute Stroke Protocol

tPA Patient Information Sheet and Consent Form (PDF)

Disclaimer

This protocol was developed by the Stroke Service and members of the Stroke Taskforce at Boston Medical Center and outlines the major responsibilities for the urgent evaluation and treatment of acute stroke patients who present to the ED.

This information is intended to be used only as a medical and educational reference tool. It does not replace or overrule the treating physician's judgment or diagnosis. We tried to keep the information as accurate as possible and therefore disclaim any implied warranty or representation about its accuracy or appropriateness for a particular purpose. This stroke protocol is subject to change without notice.

* DPH stroke care recommendations modified for BMC.

Guidelines for Use of Intravenous tPA in Acute Ischemic Stroke

Approved FDA use for LESS than 3.0 hours from initial symptoms
Off-label use for 3 to 4.5 hours (see additional warnings box below)

A.  Indications

• New symptomatic ischemic stroke with clearly defined onset AND
• Onset of symptoms to tPA < 3.0 hours (3 to 4.5 hours with warnings below) AND
• Non-contrast CT showing no intracranial hemorrhage or well-established acute infarct (>1/3 MCA territory) AND
• Patient evaluated by in-house neurology Fellow or Resident and tPA approved by stroke attending (via phone or in person)

B.  Contraindications

• Age < 18
• CT scan findings (intracranial hemorrhage, or major acute infarct signs)
• Suspicion of subarachnoid hemorrhage (even if head CT is negative for hemorrhage)
• Recent (within 3 months) major surgery or trauma (discuss with Attending)
• History of intracranial hemorrhage or brain aneurysm or vascular malformation or brain tumor (May consider IV tPA in patients with CNS lesions that have a very low likelihood of hemorrhage, such as small unruptured aneurysms or benign tumors with low vascularity)
• Known bleeding diathesis OR
  1. Current use of oral anticoagulants with INR > 1.7 or PT > 15 seconds
  2. Use of heparin within 48 hours preceding onset of stroke AND prolonged aPTT at time of presentation
  3. Platelets <100,000
  4. Internal hemorrhage (GI hemorrhage, urinary tract hemorrhage) < 3 weeks
  5. Dabigatran use in the past 48 hours (if last dose >48 hours, confirm normal renal function [creatinine clearance >50 mL/min] and normal coagulation [aPTT, INR, platelet count] before tPA administration).
  6. Low molecular weight heparin use (i.e.- Lovenox) in the past 24 hours.
• Persistent systolic BP >185 mm Hg or diastolic BP >110 mm Hg despite treatment.

C.  Warnings (risks must be weighted against anticipated benefits)

• MI within last 2 months (with normal TTE)
• Current use of oral anticoagulants with INR > 1.5 or PT > 15 seconds
• Recent stroke (within one month & depending on type & size)
• Minor neurological deficit or rapidly improving symptoms
• High likelihood of left heart thrombus
• Aortic dissection
• Evidence of infarction of > 1/3 of the MCA territory on CT
• Severe neurological deficit (NIH stroke scale score >22)
• Seizure at stroke-onset
• History of IVDA and/or suspicion for endocarditis
• Tox-screen positive for ETOH, cocaine, opiates, or amphetamines (if available, but should not delay  tPA protocol)
• Subacute bacterial endocarditis
• Acute pericarditis
• History of hemorrhagic diabetic retinopathy
• Significant hepatic dysfunction with abnormal INR
• Pregnancy
• Sickle cell disease
• Arterial puncture at non-compressible site < 1 week
• Blood sugar < 50 or > 400 mg/dL

D.  Not a contraindication

• Current aspirin, NSAID or antiplatelet drugs (dipyridamole, ticlopidine, clopidogrel)
• History of PUD (not currently active [>3 months])

E.  For those patients presenting with a suspected stroke to the Emergency Room:

1. EMT/Triage: alert EM-MD and stroke fellow (pager 1620)
2. Patient is transferred/assigned to the Trauma Room or Acute Side
3. EM/MD: ORDER STAT HEAD-CT (non-contrast enhanced) AND STAT NEURO-CONSULT [if NIHSS >8, order STAT CTA for patients who could be candidates to bridge from iv tPA to intra-arterial intervention- DO NOT DELAY tPA TO COMPLETE THE CTA]
4. RN/MD:
   - Establish 2 IV sites, including stat 18 gauge antecubital IV for CTA, start 0.9% NS pre-hydration according to recommendation under Section I.4 below.
   - Cardiac monitor, pulse oximeter, continuous vital signs
   - 12 lead EKG
   - Clinical evaluation for active illicit drug use (toxicology screen) or ETOH intoxication
   - Obtain patient weight early
   - Notify pharmacy early regarding potential tPA preparation.
5. STAT Labs: PTT, INR, CBC (without diff.), electrolytes, BUN, creatinine, CK & troponin, glucose, type & hold. Call Hematology lab to notify this is a stroke patient, place stroke stickers on tubes.
6. t-PA is approved by stroke attending or ED attending and Stroke Fellow.
7. Admit to ICU

F.  For those patients with a suspected stroke while hospitalized

1. Activate the Acute Stroke Team (1620); Have unit secretary page Rapid Response Team (help with IVs, tPA, transport to ICU). tPA can be given by the Stroke Service, CCRN, ICU nurse, or ED nurse.
2. Order a stat head-CT (non-contrast enhanced), CTA if NIHSS >8.
3. Order stat blood tests: PTT, INR, CBC (without diff.), electrolytes, BUN, creatinine, CK & troponin, glucose, type and hold
4. t-PA approved by stroke attending
5. Transfer patient to ICU
6. RN/MD (as above)
   - Establish 2 IV sites, including stat 18 gauge antecubital for CTA, start 0.9% NS at 80 cc/hour as prehydration in anticipate of CTA
   - Cardiac monitor, pulse oximeter, monitor vital signs
   - If patient is candidate for IA intervention, foley catheter

G.  Once tPA has been started –

• Do not perform for 24 hours post tPA unless procedure is life-saving: Arterial or central venous punctures/lines, IM injections, nasogastric tubes, Foley catheters
• Place the patient on anticoagulation precautions until 24 hours after the infusion
• Do not give any antithrombotic drugs (including heparin, warfarin, aspirin, clopidogrel, dipyridamole, ticlopidine, or NSAIDS x 24 hrs)
  

H.  Administration

• The stroke fellow may utilize a phone consultation with the stroke attending prior to administering IV tPA
• Administer tPA in monitored setting (unit bed or emergency room)
• Mix two 50 mg tPA vials with 50 mL normal saline each --> one mL solution contains one mg tPA for a total of 100mg in 100mL of solution.
• Estimate total body weight (if not measured on admission)
• Calculate TOTAL tPA DOSE: 0.9 mg per kg (not to exceed 90 mg total dose)
   - Give 10% as IV bolus
  - Give other 90% as IV infusion over 60 minutes
• Vital signs and neurochecks at least every 15 min for first 2 hours (including NIHSS scores- document in SCM note).
• Treat systolic BP if it rises to >180 mm Hg or diastolic BP >105 mm Hg for more than 15 minutes 
• Avoid BP decrease <160/ 85 mm Hg
  

t-PA Dosing (estimated weight)

Print tPA Dosing Chart (HTML)

Download tPA Dosing Chart (PDF)

"If the patient has a significant neurological deficit (ie NIHSS > 10) and/or CTA demonstrates proximal vessel occlusion, the neurointerventional team should be activated early (pager 2645 or COIL), i.e. as soon as the decision to give tPA has been established.

I.  Monitoring:

1. Admit to ICU and monitor patient in ICU for a minimum of 24 hours.
   • Unless the patient is unstable, notify ED attending and bed control RN that patient should be admitted to the neurocritical care service in the neuro-ICU (ENC 3 West).  The patient will be co-managed by the MICU service.  Patients undergoing acute endovascular or surgical treatment will be admitted to the HAC SICU.  The ED Neurology resident must sign out to the appropriate admitting ICU resident
     
     
2. Blood pressure monitoring:
   1. During the first 24 hours after tPA, monitor BP:
      - Every 15 minutes for 2 hours after starting the infusion, then
      - Every 30 minutes for 6 hours, then
      - Every 60 minutes until 24 hours after starting treatment
      
      
3. If systolic blood pressure is >180 mmHg or if diastolic blood pressure is >105 mmHg for 2 or more readings 5 to 10 minutes apart, the following is recommended:
   
   1. First tier intervention:  Give IV labetalol 10 mg over 1 to 2 minutes. Labetalol may be repeated up to 3 doses every 10 to 20 minutes (doubling doses if needed depending on effect of preceding dose; eg. 1st dose-10mg, 2nd dose- 20mg, 3rd dose- 40mg, then consider drip)
      - For heart rate<60/minute, use hydralazine 5-20mg intravenous over 1-2 minutes every 20-30 minutes.  After second bolus, consider second line intervention.
      - Monitor blood pressure and neurologic exam every 15 minutes during treatment and observe for development of hypotension for all 3 tiers of BP interventions.
   2. Second tier intervention:  If 3 doses of labetalol or hydralazine bolus or 30 minutes pass without sufficient BP control, the next step should be a nicardipine drip.
   3. Third tier intervention:  If nicardipine drip fails, then the next step should be a labetalol drip.
      
      **To avoid worsening of cerebral ischemia, target BP of 155-175/85-100.
4. Use 0.9% NS only, as needed (avoid hypotonic solutions). Initiate fluid hydration in the ED with 500cc bolus over the 1st hour, then NS at 100cc/h except in those patients who have a contraindication (pulmonary edema, renal failure, know CHF/LVEF<40%/mod-severe diastolic dysfxn)
   
   
5. Further management as directed by the neurocritical care service.

REFERENCES

De Smedt A, De Raedt S, Nieboer K, De Keyser J, Brouns R.  Intravenous thrombolysis with recombinant tissue plasminogen activator in a stroke patient treated with dabigatran. Cerebrovasc Dis. 2010;30:533–534

Ganetsky M, Babu KM, Salhanick SD, Brown RS, Boyer EW. Dabigatran: review of pharmacology and management of bleeding complications of this novel oral anticoagulant. J Med Toxicol. 2011 Dec;7(4):281-7.

Watanabe M, Siddiqui FM, Qureshi AI. Incidence and management of ischemic stroke and intracerebral hemorrhage in patients on dabigatran etexilate treatment. Neurocrit Care. 2012 Feb;16(1):203-9.

Alberts M., Bernstein R., Naccarelli G., Garcia D.  Using Dabigatran in Patients With Stroke A Practical Guide for Clinicians.  Stroke. 2012; 43: 271-279

del Zoppo G, Saver J, Jauch EC, et al. Expansion of the Time Window for Treatment of Acute Ischemic Stroke WithIntravenous Tissue Plasminogen Activator. A Science Advisory From the American Heart Association/American StrokeAssociation. Stroke 2009; 40: 2945.

De Silva DA, Manzano JJ, Chang HM, Wong MC. Reconsidering recent myocardial infarction as a contraindication for IV stroke thrombolysis. <http://www.ncbi.nlm.nih.gov/pubmed/21490319> Neurology 2011;76:1838-40.

Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359:1317-29.

The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-7.

Rost NS, Masrur S, Pervez MA, Viswanathan A, Schwamm LH. Unsuspected coagulopathy rarely prevents IV thrombolysis in acute ischemic stroke. Neurology. 2009 Dec 8;73(23):1957-62. Epub 2009 Nov 25.

Selim M, Kumar S, Fink J, Schlaug G, Caplan LR, Linfante I. Seizure at stroke onset: should it be an absolute contraindication to thrombolysis? Cerebrovasc Dis. 2002;14(1):54-7.

Addendum A: DABIGATRAN (PRADAXA):

1. Drug information-
   • Direct thrombin inhibitor (like argatroban, hirudin, bivalirudin) indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.
     
     
2. Dose-
   • Oral (first oral anticoagulant other than Coumadin)
   • Twice daily dosing (vs Coumadin once daily)-
     a. For patients with CrCl >30 mL/min: 150 mg orally, twice daily
     b. For patients with CrCl 15-30 mL/min: 75 mg orally, twice daily
   • Instruct patients not to chew, break, or open capsules
   • Half-life 12-17 hours (vs Coumadin 40 hours)
   • Therapeutic within 30 minutes (vs Coumadin 5 days) with peak levels at 1-3 hours
   • Steady-state reached within 2-3 days
   • WARNING- avoid co-administration with rifampicin (increase removal)
     
     
3. Lab considerations-
   • NO LAB monitoring needed! (unlike Coumadin)
   • Prolongs PTT 2 fold at peak
   • Trough PTT 12 hrs later = 1.5 fold prolonged
   • INR may or may not be prolonged
   • Thrombin time is very sensitive- a normal result indicates drug is essentially gone
     
     
4. Important notes-
   • Renal clearance (unlike Coumadin)
   • DIALYSIS removes dabigatran; probably also oral charcoal can be used
   • Before surgery: Stop 1-2 days if normal kidneys (creatinine clearance ≥50 mL/min) vs Coumadin stop 3-5 days
   • As of yet, there is no solid evidence to guide management of bleeding complications; management should start with local control of bleeding when possible and transfusion of pRBCs if needed. Transfusion of FFP would not be expected to help control bleeding. Limited and mixed data exist for transfusion of factor VIIa and prothrombin complex concentrates; these therapies should be considered as well as dialysis, which will increase elimination in patients with life-threatening or closed-space bleeding due to dabigatran.
   • The RE-LY study randomly assigned 18,113 patients who had non-valvular AF and ≥1 stroke risk factors to either open-label warfarin or dabigatran; 2 doses of dabigatran were tested. The rate of major bleeding was 3.36% per year in the warfarin group as compared with 2.71% per year in the group receiving 110 mg twice a day of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg twice a day of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group as compared with 0.12% per year with 110 mg twice a day of dabigatran (P<0.001) and 0.10% per year with 150 mg twice a day of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group as compared with 3.75% per year with 110 mg dabigatran (P=0.13) and 3.64% per year with 150 mg dabigatran (P=0.051).