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Interventions for Interventions for Acute Ischemic StrokeAcute Ischemic Stroke

Lisa Bellamy, RN, CPHQ, Managing Director –Stroke Care Network

Bill Singletary, RN, BA, BSN, MBM, Director Clinical Documentation & Specialty Certification, Stroke Program Coordinator – The Medical Center at Bowling Green

Objectives1. Discuss the use of IV t-PA and indications for

stroke patients

2. Discuss interventions outside of the three hour symptom onset available for stroke patients, including IA t-PA, interventional procedures and surgery

Epidemiology:Epidemiology: Stroke Stroke in the USin the US• ~800,000 new or recurrent

strokes each yearo One every 40 seconds o ~85% are ischemic stroke

• Stroke is a leading cause of disability o Over 6.6 million >20 years of age have

h d t k

• 10% Return to normal

• 48% Weak on one side

• 22% Unable to walk

• 38% Complete or partial

Mozaffarian, et. al., 2015

had a strokeo Projections show by 2030, an

additional 3.4 million will have stroke

• Stroke is the 5th leading cause of death in the US o Every 4 minutes someone dies of

stroke

38% Complete or partial dependence

• 15% Aphasic

• 32% Clinically depressedNational Stroke Association. The Stroke/Brain Attack Report’s Handbook, 1997

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The Stroke Belt

International Classification of Diseases, 10th Revision codes for stroke: 160-169. National vital Statistics System and the US Census Bureau.Stroke death rates, 2000-2006: adults > 35 yrs, by county.

Kentucky Stroke Care Disparitieso Cultureo Education Risk factors Warning signs Treatments

o Geography - Remote locationso Lifestyle choices - Food choices, low activity level,

high smoking rateso Socio-economic statuso Few stroke-care experts

Types of Stroke

•Subarachnoid – 3%•Intraparenchymal – 10%Other 4%

Cryptogenic 26%Lacunar 21%

Cryptogenic 26%

Hemorrhagic 13%(TOAST) Trial of Organization 10172 in Acute Stroke Treatment, Lovenox vs ASA, 3rd

version of NIHSS checked, Dec 1990 – Dec 1997

Ischemic 87%

Atherosclerotic 17% Cardioembolic 17%

American Heart Association/American Stroke Association 2011, Albers GW, et al. Chest. 2004;126:483S-512S.

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Ischemic Penumbra: Hypo-perfused Area of Focal Ischemia That May Be

Salvaged by Timely Intervention

Infarct<8 mL/100 g/min

Penumbra8-20 mL/100 g/min Normal

50 mL/100 g/minAhmed, 2001

Core Infarct Penumbra Tissue Left to Save

Saver, 2006

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Treatment Windows Treatment Windows from Time from Time Last Known WellLast Known Well

• Intravenous (IV) Activase® (Alteplase) (rt-PA) is FDA approved within 3 hours and recommended by AHA and AAN within 4.5 hours

• Mechanical thrombectomy is recommended for patients with large vessel occlusion in whom groin puncture can be obtained within 6 hours

• Multiple randomized controlled trials have shown endovascular thrombectomy to be significantly beneficial in the treatment ofthrombectomy to be significantly beneficial in the treatment of Emergent Large Vessel Occlusion (ELVO)o The AHA Guidelines recommend utilization of thrombectomy for patients

within 6 hours, but stipulate that appropriate candidates may exist far outside that window

o Neuro-interventionalists are increasingly using imaging rather than time to determine candidacy for intervention

Demaerschalk, et. al., 2016 and Powers, et. al., 2015

Standard of Care: Treatment Windows from

Time Last Known Well

• FDA approved • Evidence-

IV tPA• Evidence-

based • FDA

Mechanical Retrieval • Evidence-

basedapproved• 3 Hours

IV tPA

Evidencebased

• 4.5 Hours

based• 6 Hours

IA tPA

FDA Approved

• 8 Hours

based• 12 hours

Mechanical Retrieval

Endovascular intervention may be considered beyond 12 hours

ED Stroke AlertED Stroke AlertDoor to first physician contact

10 minutes (UK 5 minutes)Door to initiation of CT Scan

25 minutesInterpretation of CT Scan

20 minutes after test completion20 minutes after test completion Door to EKG, Labs and Chest x-ray result

45 minutesDoor to Needle Time

<60 minutes

Jauch , et al., 2013

Target treatment with rt-PA should be within 1 hour of the patient’s arrival in the ED

(Class I, Level of Evidence A)

AHA/ASA Guideline Recommendations

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Time is Brain: 2million neurons/minuteEmergency Stroke Alert

• ABCs

• History: TIME – last known normal

• Physical Exam: Baseline NIHSS

• Imaging: CT/CTAo CT rules out hemorrhageo CTA establishes location of occlusiono Perfusion

Activase AlteplaseA Recombinant Tissue Plasminogen Activator (rt-PA, aka t-PA)

• The only FDA approved thrombolytic agent for treatment of strokeo Approved June 1996

• An enzyme which has the property of fibrin-enhanced conversion of plasminogen to plasmin

• Binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin

• Initiates local fibrinolysis

“Stroke Clot Buster”

Overall Benefits and Overall Benefits and Risk Risk of of IV IV rtrt--PA PA for for StrokeStroke

• Benefit: neurologically normal at 3 monthso 55% relative increaseo 12% absolute increase

• Very robust effect: NNT = 8

NINDS rt-PA Stroke Study Group. N Engl J Med. 1995;333:1581-1587.

Adams HP Jr, et al. Stroke. 2003;34:1056-1083.

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Using rt-PA in Routine Clinical Practice• Rate of ICH at 36 hours: 4%-6.4%

o No increase in 90-day mortality compared to placebo group

• Overall risk of complications, including ICH increases with protocol violations:o Time window violationso Poor blood pressure controlo Poor blood pressure controlo Using prohibited agentso Wrong doseo Elevated blood sugar also increases risk

• Risk of ICH can be reduced by closely following the rt-PA protocol

It is important to utilize a

rt-PA Checklistas approvedas approved

at your facility

• Diagnosis of ischemic stroke causing measurable neurological deficit

• Computed tomography (CT) rules out hemorrhage or non-stroke cause of deficit

Indications for IV Indications for IV rtrt--PAPA

• 18 years old or older

• Time to treatment less than 3 hours of confirmed time Last Known Well, or 4.5 hours with additional considerations

Demaerschalk, et al., Stroke. 2016;47:581–641

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Current intracranial hemorrhage Suspicion of subarachnoid hemorrhage Intra-axial intracranial neoplasm History of intracranial/intraspinal surgery within 3 months Severe head trauma within 3 months Gastrointestinal malignancy or active internal bleeding within 21 days Bleeding diathesis

Platelets less than 100,000/mm3

International Normalized Ratio (INR) greater than 1.7 Activated partial thromboplastin time greater than 40 seconds

ContraindicationsContraindications

Activated partial thromboplastin time greater than 40 seconds Prothrombin time greater than 15 seconds

Warfarin use with INR greater than 1.7 Low molecular weight heparin within 24 hours (prophylactic and treatment doses) Direct thrombin inhibitors or direct factor Xa inhibitors (unless not taken within 48 hours or absence of

therapeutic effect on appropriate screening tests) Sustained/uncontrolled BP more than 185/110 mmHg (refractory to antihypertensives) Acute bacterial endocarditis Aortic Arch dissection Demaerschalk, et al., Stroke. 2016;47:581–641

History of intracranial hemorrhage History of ischemic stroke within 3 months (considerations: size, location & timing of prior stroke) Extensive regions of clear hypoattenuation on initial CT Unruptured/unsecured AVM >10 mm unruptured/unsecured aneurysm Major surgery within 14 days Major trauma within 14 days Arterial puncture of noncompressible vessel within 7 days Hi f i i l i i h h

Warnings/Use Clinical Judgment Warnings/Use Clinical Judgment

History of gastrointestinal or genitourinary hemorrhage Malignancy with life expectancy less than one year History bleeding diathesis Hemorrhagic ophthalmic condition Acute pericarditis History of myocardial infarction involving left anterior myocardium within 3 months Left sided heart thrombus Pregnancy

Demaerschalk, et al., Stroke. 2016;47:581–641

• 3 hour window contraindications and warnings continue to apply, PLUS:

NIH St k S l (NIHSS) t th 25

Additional Additional Warning Warning for 3for 3––4.5 hour Window4.5 hour Window

NIH Stroke Scale (NIHSS) greater than 25- benefit is uncertain due to lack of evidence- these may be candidates for thrombectomy

Demaerschalk, et al., Stroke. 2016;47:581–641

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rt-PA Kit:• Activase Vial• Vial of Sterile Water (USP)

T f d i

Handwashing Gloves

10 Easy Steps for Reconstitution

• Transfer device

Other Items Needed:• Alcohol swabs• 2 Syringes

1. Bolus2. Discarded Activase

• Large bore needles

Remove caps from each vial

Remove transfer device from wrapper

Swab the top of each vial with alcohol wipe

Insert piercing pin vertically into the center of

Keep vial upright

& remove the cap from one end the stopper of the sterile water

Turn Activase vial up-side-down & pierce device in the center

Invert and allow sterile water to flow into Activase vial

~2 minutes

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Remove empty sterile water vial & transfer device

Mix with a gentle swirl – do not shake

Slight foaming is normal

Allow to sit undisturbed for several minutes

Visually inspect for particulate matter & discoloration before administration

• N o medi cat i on shoul d be added to Ac t i vase• Al l unused medi cat i on shoul d be d i scarded

Activase will remain stable at room temperature for up to 8 hours

rtrt--PA DosePA Dose0.9 mg/kg (Maximum total dose of 90 mg)

All excess rt-PA needs to be removed from vial prior to dose preparation to prevent excess infusion

10% of the total calculated dose administeredas an initial IV bolus over 1 minute

drip the remainder over 60 minutes

IV normal saline flush infused at the same rate immediately following rt-PA administration, in order to clear the line and infuse entire calculated dose

IV IV rtrt--PA PA Considerations: Considerations: New AnticoagulantsNew Anticoagulants

• Dabigatran (Pradaxa)• Rivaroxaban (Xarelto)

• Consensus Statement:o Last dose within 48 hours = Contraindication to IV rt-PAo Or presence of therapeutic effect on appropriate screening

tests = Contraindication to IV rt-PA

• Apixaban (Eliquis)• Edoxaban (Savaysa)

tests = Contraindication to IV rt-PA

• If reason to suspect abnormal platelet counts or coagulation studies:o aPTT for heparin; PT/INR for warfarin; Anti-factor Xa for

LMWH; direct thrombin assay for dabigatran and direct factor Xa assays for rivaroxaban, edoxaban, & apixaban

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IV IV rtrt--PA Considerations: PA Considerations: BP ManagementBP Management

• IV t-PA is recommended in patients whose blood pressure can be lowered safely (to <185/110 mm Hg) with antihypertensive agents, with the physician assessing the stability of the blood pressure before starting IV rt-PA o (C-I, L-B)

• If medications are given to lower blood pressure the clinician• If medications are given to lower blood pressure, the clinician should be sure that the blood pressure is stabilized at the lower level before beginning treatment with IV rt-PA and maintained below 180/105 mm Hg for at least the first 24 hours after IV rt-PA treatmento (C-I, L-B)

C=Class, L=Level of Evidence Demaerschalk, et al., Stroke. 2016;47:581–641

IV IV rtrt--PA Considerations: PA Considerations: LabsLabs

• Given the extremely low risk of unsuspected abnormal platelet counts or coagulation studies in a population, it is reasonable that urgent IV rt-PA treatment not be delayed while waiting for y ghematologic or coagulation testing if there is no reason to suspect an abnormal test o (C-IIa, L-B)

C=Class, L=Level of Evidence Demaerschalk, et al., Stroke. 2016;47:581–641

IV IV rtrt--PA Consideration: PA Consideration: ConsentConsent

• IV t-PA in suspected stroke patient is considered emergent treatment. A separate consent is NOTrequired, unless required by your organizationo (C-1, L-C)

• Required documentation includes that “risks, benefits and alternatives” were explained and verbal or written consent obtained (when possible)

C=Class, L=Level of Evidence Demaerschalk, et al., Stroke. 2016;47:581–641

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During and 24 hours After IV During and 24 hours After IV rtrt--PAPA

• Avoid:o Blood pressure elevations more than SBP 180 and DBP 105o Anticoagulants, antiplatelets, antithrombotics,

thrombolyticso Invasive procedures, invasive lines, catheters or tubes

l d d di ll i ti unless deemed medically imperativeo Mobilization

safety is maximized when on bedrest precautions

Keep NPONPO until infusion complete & no side effects are observed,and until dysphagia screen or evaluation passed after infusion

MMonitoring onitoring DDuring uring and and After After IV tIV t--PAPA

• “Enhanced neurological check”/abbreviated NIHSS and vital signs:o Every 15 minutes for 2 hours, then every 30 minutes for 6

hours, every 1 hour for 16 hours, every 2 hours for 24 hours, every 4 hours for 24 hours, after the initial 72 hours: every 8 hours and prn until discharge

• NIHSS:o Baseline at arrival, just prior to bolus, repeat at 30 minutes

(half way through infusion), at 60 minutes (end of infusion) Expert Consensus Recommendation: then every 2 hours for 48

hours, every 4 hours for 24 hours, after initial 72 hours: every 12 hours and prn with any neurological decline until discharge

Monitoring During and After IV t-PA• Bleeding

o Intracranial bleedingo Internal bleeding

Intracranial and retroperitoneal sites GI, GU or respiratory tracts

o Superficial bleeding

• Orolingual AngioedemaOrolingual Angioedema

o Angioedema is a rare (1-2%), but potentially serious complication especially experienced by those on ACE inhibitors

o Orolingual angioedema can be asymmetric and can occur contralateral to the ischemia

o Can be treated with epinephrine, antihistamines and corticosteroids

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Management of Hemorrhage After Management of Hemorrhage After rtrt--PAPA

• If bleeding is clinically suspected: sudden headache, deterioration in mental status, hypotension, etc.

o Discontinue rt-PA infusion immediatelyo Emergent CT scan of head and/or body where

hemorrhage suspectedhemorrhage suspectedo STAT Prothrombin Time (PT), Partial Thromboplastin

Time (PTT), platelet, fibrinogen, type/crosso Prepare 6-8 units of cryoprecipitateo Prepare 6-8 units of platelets

The Brain Attack Coalition: t-PA Stroke Study Group Guidelines, 2011

• If hemorrhage present:

o Administer cryoprecipitate or platelets as neededo STAT neurosurgical consultation if intracranial

hemorrhage present

Management of Hemorrhage After Management of Hemorrhage After rtrt--PAPA

o Consider STAT surgical consultation if extracranialhemorrhage present

o Consider second CT scan of hemorrhage to assess progression

The Brain Attack Coalition: t-PA Stroke Study Group Guidelines, 2011

Additional InterventionsAdditional Interventions• HOB 30 degrees• Cardiac monitoring• Aspiration/fall/seizure precautions• Continual assessment and treatment of:

o ABC’so Enhanced Neurological Checko NIHSSo Vital Signso Normothermiao Dysphagiao 0.9% saline at 50-100 cc/hour (no D5W)o O2 per nasal cannula to keep Sats > 94%

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30-50% of strokes are large vessel occlusions

What Constitutes Large Vessel?

Vessels:- ICA- A1- M1- M2- Basilar- Vertebral

30-50% of strokes are large vessel occlusions

New Designation: ELVO

• Stroke process due to occlusion of ‘large’ vessel

• ANALOGY:o STEMI = ST Elevation Myocardial Infarctiono ELVO = Emergent Large Vessel Occlusion

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ELVO Trials

• MR-CLEAN

• EXTEND-IA

• SWIFT PRIME

• ESCAPE

Halted early for efficacy

Intra-arterial (IA) rt-PA• Angiograph catheter

• 6 hourso Not FDA approvedo Is given based on clinical trial data

• 20-30% recanalization rate

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Mechanical ThrombectomyMerci Retrieval System R

Penumbra Retrieval Device Solitaire TM FR

Trevo R

12 Hours with ELVO

Extracranial Angioplasty and Stenting• Usually for prevention

• Acute Ischemic Stroke:o Etiology of stroke is cessation of

flow in the extracranial carotid or vertebral arteryvertebral artery Atherosclerosis Dissection

o Catheter access to intracranial thrombus is impeded by extracranial stenosis or occlusion

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Decompressive Hemicraniectomy

• Usually large volume or posterior fossa infarctions• Can reduce mortality from 80% to ~20%

References1. Berkhemer, O., & Et. al.,. (2015). A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. The New England Journal of

Medicine, 372(1), 11-20. doi:10.1056/NEJMoa1411587 http://www.nejm.org/doi/full/10.1056/NEJMoa1414905#t=article

2. Goyal, M., & Et. al.,. (2015). Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke. The New England Journal of Medicine, 372(11), 1019-1030. doi:10.1056/NEJMoa1414905 http://www.nejm.org/doi/full/10.1056/NEJMoa1414905#t=article

3. Fraser, J. (Director) (2015, July 24). Opening the Floodgates: Update on ground-breaking changes in management of acute stroke. Network Summit. Lecture conducted from Stroke Care Network, Lexington, KY.

4. AHA/ASA Guideline: Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association, Edward C. Jauch, et. al., on behalf of the American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Peripheral Vascular Disease, and Council on Clinical Cardiology. Stroke. 2013;44:870-947, published online before print January 31 2013, doi:10.1161/STR.0b013e318284056a http://stroke.ahajournals.org/content/44/3/870.fullp // j g/ / / /

5. AHA Statistical Update: Heart Disease and Stroke Statistics—2015 Update: A Report From the American Heart Association, DariushMozaffarian, et. al., on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee, Circulation. 2015;131:e29-e322, published online before print December 17 2014, doi:10.1161/CIR.0000000000000152 http://circ.ahajournals.org/content/131/4/e29.full

6. Powers, W., & Et all. (2015, June 15). 2015 AHA/ASA Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment. Retrieved July 31, 2015. http://stroke.ahajournals.org/content/early/2015/06/26/STR.0000000000000074.full.pdf+html

7. Yayan, J. (2013). Onset of Orolingual Angioedema After Treatment of Acute Brain Ischemia with Alteplase Depends on the Site of Brain Ischemia: A Meta-analysis. North American Journal of Medical Sciences, 5(10), 589–593. doi:10.4103/1947-2714.120794 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842699/