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Acute Ischaemic

Stroke

Hospital Kuala Lumpur Acute

Ischaemic Stroke Thrombolysis

Initiatives (HASTE)

Dr Mahathar Abd Wahab,

MBChB, M Med (Emerg. Med), Cert ML

Consultant Emergency Physician

Emergency and Trauma Department,

Hospital Kuala Lumpur

Stroke Epidemiology

3rd most common cause of death in developed countries, exceeded only by coronary heart disease and cancer

In Malaysia, top five leading causes of death with 8.43 per 100,000 population (MOH 2009)

795,000 new or recurrent strokes occur per year in the US, accounting for approximately 1 in 18 deaths

The prevalence of stroke in the US is about 7 million (3.0%) at an estimated cost in 2010 of 73.7 billion US-$

In Europe, the incidence of stroke varies from 101.1 to 239.3 per 100,000 in men and 63.0 to 158.7 per 100,000 in women

The estimated cost of stroke in Europe in 2010 was approx. € 64.1 billion

In China, the prevalence of stroke ranges between 1.8% (rural areas) and 9.4% (urban areas)

Worldwide, China has one of the highest rates of mortality (19.9% of all deaths in China), along with Africa and parts of South America

Gustavsson et al. Eur Neurpsychopharmacol 2011;21:718-779.

AHA and Stroke Statistics Writing Group. Circulation 2010;123:e1-e192.

EROS Investigators. Stroke 2009;40:1557-1563.

Sousa et al. Lancet 2009;374:1821-1830. The Atlas of heart disease and stroke, WHO 2004.

Ischaemic stroke

88%

Stroke Types and Incidence

Albers et al. Chest 2004;126 (3 Suppl):438S-512S.

Thom et al. American Heart Association. Circulation 2006;113:e85-e151.

HaemorrhagicOther

5%

Cryptogenic30%

Cardiacembolism

20%

Small vesseldisease

“lacunes”25%

Atheroscleroticcerebrovascular

disease20%

12%

Stroke : Definition

Clinical syndrome characterized by;

rapidly deteriorating symptoms and/or signs of

focal, at times, global loss of cerebral function,

with symptoms lasting > 24 hours or leading to

death,

with no apparent cause other than that of

vascular origin

Pathophysiology

Stroke is an Emergency

Potential to Reverse Neurologic Impairment With

Thrombolytic Reperfusion

Saver. Stroke 2006;37:263-266.

González. Am J Neuroradiol 2006;27:728-735.

Donnan. Lancet Neurol 2002;1:417-425.

An untreated patient loses

approximately 1.9 million

neurons every minute in

the ischaemic area

Reperfusion offers the

potential to reduce the

extent of ischaemic injury

Ischaemic core

(brain tissue

destined to die)

Penumbra

(salvageable

brain area)

“Time is Brain!”

Saver. Stroke 2006;37:263-266.

Estimated Pace of Neural Circuitry Loss In Typical Large-Vessel

Supratentorial Acute Ischaemic Stroke

Neurons Lost Synapses Lost Myelinated Fibres Lost Accelerated Aging

Per Stroke 1.2 billion 8.3 trillion 7140 km 36 y

Per Hour 120 million 830 billion 714 km 3.6 y

Per Minute 1.9 million 14 billion 12 km 3.1 wk

Per Second 32,000 230 million 200 m 8.7 h

Minutes Hours Days

Inflammation

Peri-infarct

depolarisations

Excitotoxicity

Impact

Apoptosis

Time

Guidelines

AHA

(The American Heart Association)www.americanheart.org

ESO

(The European Stroke Organisation)www.eso-stroke.org

AHA/ASA Guidelines

Recommendations on Emergency Systems

Suspected acute stroke – be identified rapidly by dispatch centres, which should dispatch the highest level of care available in the shortest possible time

EMS should briefly assess the patient on site (Class I, LOE B)

EMS should begin initial stroke management in the field (Class I, LOE B)

Patients should be transported rapidly for evaluation and treatment to the closest stroke facility (Class I, LOE B) and the EMS should inform the ED prior to arrival

Telemedicine can be an effective method to provide expert stroke care to patients located in rural areas (Class IIA, LOE B)

Pre-hospital providers, emergency physicians, and stroke experts should collaborate to develop training, assessment and transportation protocols

Acker et al. Stroke 2007;38:3097-3115.

Adams et al. Stroke 2007;38:1655-1711.EMS, emergency medical services

ED, emergency department

AHA/ASA Guidelines

Recommendations on Stroke Centres

Creation of primary stroke centres is strongly

recommended (Class I, LOE B)

Development of comprehensive stroke centres is

recommended (Class I, LOE C)

Certification of stroke centres by an external body

(e.g. JCAHO) is encouraged (Class I, LOE B)

Patients with suspected stroke should bypass

hospitals without stroke resources and go to the

closest facility capable of treating acute stroke (Class I, LOE B)

Adams et al. Stroke 2007;38:1655-1711.JCAHO, Joint Commission on the

Accreditation of Healthcare Organisations

AHA Guidelines for Cardiopulmonary Resuscitation and

Emergency CV Care

Several studies a higher likelihood of good to excellent functional outcome when rt-PA is administered to adult patients with acute ischaemic stroke within 3 hours of symptom onset

Treatment of carefully selected patients with acute ischaemic stroke with IV rt-PA between 3 and 4.5 hours after onset of symptoms has also been shown to improve clinical outcome, although the degree of clinical benefit is smaller than that achieved with treatment within 3 hours

Administration of IV rt-PA to patients with acute ischaemicstroke who meet the NINDS or ECASS 3 eligibility criteria is recommended if rt-PA is administered by physicians in the setting of a clearly defined protocol, a knowledgeable team, and institutional commitment(Class I, LOE B)

Jauch et al. Circulation 2010;122(suppl.3):S818-S828.

ESO Guidelines for the Management of Ischaemic

Stroke and Transient Ischaemic Attack

In patients admitted within 3 hours of stroke onset brain CT should be obtained to guide routine thrombolysis treatment with rt-PA (Class I, Level A)

I.V. rt-PA (0.9 mg/kg body weight, max. 90 mg), with 10% of the dose given as a bolus followed by a 60-minute infusion, is recommended within 4.5 hours of onset of ischaemic stroke (Class I, Level A)

The use of multimodal imaging may be useful for patient selection for thrombolysis but is not recommended for routine clinical practice (Class III, Level C)

ESO Guidelines 2009 Update. www.eso-stroke.org

ESO Guidelines: Recommendations for

Stroke Services and Stroke Units

All stroke patients should be treated in a stroke unit (Class I,

Level A)

Acute stroke patients should have access to high technology

medical and surgical stroke care when required (Class III,

Level B)

The development of clinical networks, including

telemedicine, is recommended to expand access to high

technology specialist stroke care (Class II, Level B)

ESO Guidelines 2009 Update. www.eso-stroke.org

Acute Ischemic Stroke - Issues

Public awareness

Delay in seeking treatment

Institutional commitment

Collaboration and multidisciplinary agreement

Financial implications

Longer hospital stays

The Initiatives

Hospital Kuala Lumpur, Kuala Lumpur, Malaysia

Raising Public Awareness

Campaigns

Target the general public as stroke witnesses

Symptom awareness

Awareness to take action

Keep the message easy

The ultimate aim is to keep the time to treatment as short as possible

Public awareness campaigns can increase ambulance dispatches for stroke

Example of a German stroke

awareness campaign

Raising Public Awareness

Acute Ischemic Stroke Thrombolysis Initiative

Multidiscipline approach

Emergency Medicine

Neurology

Neurosurgery

Radiology and Neuroradiology

Pharmacy

To achieve common goals

Development of

Critical Pathways

HASTE

CRITICAL PATHWAY(HKL – HASTE)

MECC acute stroke patients - identified rapidly by dispatch centres, which should dispatch the highest level of care available in the shortest possible time

Critical Pathway

TIME SITE ACTIVITY PERSONNEL OUTCOME

0 MECC 1. Receive Emergency Call

From Public.

2. History :

a. Facial asymmetry ,

b. Arm drift,

c. Slurred speech,

d. Time of Onset

Call Taker Time <3hrs

MECC Call Card

DISPATCH

Critical Pathway


5-30

mins

Dispatc

h/

Incident

Site

1. Scene Safety & Primary

Survey

2. Perform Cincinnati Pre

Hospital Stroke Scale: Facial

asymmetry , Arm drift,

Slurred speech, Time of

Onset

3. Prompt Transport To HKL.

4. Enroute:

a. PERFORM PRIMARY

SURVEY

b. Protect airway,

c. Assist Ventilation,

d. Oxygen Supplement if

needed

e. Monitoring & Head

elevated 15o.

PPP /SN Response

Time <

20mins

P2

Cincinnati Stroke Scale: A Checklist for Emergency

Medical Dispatchers

Govindarajan et al. BMC Neurology 2011;11:14.

Total score:

3 Clear evidence of stroke

2 Strong evidence of stroke

1 Partial evidence of stroke

0 No evidence of stroke

3-Question Checklist Score

1. Ask patient to smile

Normal 0

Slight difference 1

Obvious difference 3

Cannot complete at all

2. Ask patient to raise both arms above head

Both arms raise equally 0

One arm higher than the other 1

Cannot complete request at all

3. Ask patient to say “the early bird catches the worm”

Said correctly 0

Slurred speech 3

Garbled or not understood 3

Cannot complete request at all

Critical Pathway


15 -30

mins

Dispatch 5. Specific Assessment:

a. Age,

b. Time of onset,

c. GCS,

d. History of bedridden or

wheelchair bound,

e. history of seizure,

f. blood glucose,

g. name/ phone no of

person who can give

consent.

6. Radio in

7. Communication

• MECC to Resus

• Patient Arrival

Preparation

• Facilitate Early CT

PPP / SN Response

Time <

20mins

P2

TRIAGE COUNTER

Critical Pathway


30-35

mins

Triage

Counter

1. History :

a. Facial asymmetry ,

b. Arm drift,

c. Slurred speech,

d. Time of Onset

2. FIRST LOOK Assessment

1. Ambulating

2. Wheel Chair Bound

3. Trolley Bound

3. Three Bells

4. Transfer patient to RESUS

if time of onset <3hrs.

PPP / SN

Triage

Time onset

<3hrs

Critical Pathway – ED MO


35

min –

4.5

hours

RESUS 1. Primary Survey & stabilize

the patient.

2. Activate Stroke Team.

3. Acute Stroke Code Flow

Chart / Checklist

4. History : Ascertain time of

onset & symptoms.

5. Indications &

contraindications for

thrombolysis

6. Focal neurological signs

evidence.

7. Modified Rankin Score

8. Arrange & perform CT Brain.

MO ED

incharge of

Resus

Door to CT <

45mins

Critical Pathway – ETD MO

TIME SITE ACTIVITY PERSONNE

L

OUTCOME

<4.5

hrs

RESUS

1. Weigh The Patient

2. Venous access (at least

16G) at cubital fossa

1. Investigations (Mark

the Ix form:

Emergent Acute

Stroke

Thrombolysis) :

2. DXT stat,

3. ECG,

4. Blood Test: FBC ,

RP, COAG, LFT,

BSH,

5. CT Brain

3. Interpret CT Scan

MO ED

incharge of

Resus

SN/PPP

Emergency

Physician/

Neurologist/Ra

diologist

Door to CT <

45mins

Patient Weight

Patient Weight

Before calibration

Patient Weight

After calibration

Critical Pathway – Radiology


RESUS

(cont.)

1. Prepare machine &

perform the CT Brain

2. Radiologist to interpret CT

3. ASPECT score

4. Inform result to MO

Neurology/ED MO.

Radiology Door to CT

<45 mins

Critical Pathway – Neuro Medical


RESUS

(cont.)

1. Determine the severity of

deficit using the NIHSS

2. Thrombolysis if indicated

and no absolute

contraindication.

3. 0.9mg/kg not to exceed a

max of 90mg. 10% to be

given IV bolus over 1 – 2

mins & remaining 90% to

be given over 60 mins.

4. Keep patient NBM for 24

hours.

MO

Neuromedical

/Neurologist

Door to

Needle (DTN)

<60 mins

Critical Pathway – Resus SN


RESUS

(cont.)

1. Drug Preparation and

Dilution

2. Patient Monitoring:

a. Monitor

BP/PR/RR/SpO2

a. Every 15mins

during infusion &

b. then 30mins for

the next 2hrs.

c. Thereafter every

hour for the next

24hrs.

b. GCS monitoring every

15mins during infusion.

SN Resus /

Neuro SN

Complete

Monitoring as

per indicated

Critical Pathway


<5hrs Acute

Stroke

Ward/IC

U

1. Admit patient to ward

1. Transfer Checklist

2. Patient Monitoring

PPP/SN/PPK Checklist

before

Transfer

complete

Critical Pathway

Acute Stroke

Summary

Thank You

Other Reference

1. Special Thanks to Prof Ismail Saiboon and Assoc. Prof Dr Mohd

Idzwan Zakaria for sharing the stroke protocols from their institutions

2. UMMC – Guidelines for Thrombolysis od Acute Ischemic Stroke Patient

3. tPA Patient Information's Sheet – Boston Medical Centre

4. Acute Stroke Pathway for ED – PPUKM

5. ED PPUKM Pre hospital Stroke Guidelines

6. Use of ASPECT in Acute Ischemic Stroke

7. Acute Iscahemic Stroke Thrrombolysis Protocol – Hospital Kuala

Lumpur

Actilyse®

Product Details

Actilyse®

Actilyse®, rt-PA, is a serine protease, similar to naturally occurring tissue plasminogen activator (t-PA)

Mode of action

With high affinity, Actilyse® binds to and activates plasminogen attached to the fibrin netting of a blood clot

Plasminogen is converted to plasmin, which catalyses the breakdown of fibrin to its degradation products, resulting in break up of the clot

The affinity for freely circulating plasminogen is low, so Actilyse® has highly effective local fibrinolytic effects and relatively few systemic effects

Hoylaerts et al. J Biol Chem1982;257:2912-2919.

Impressum

Published by

Boehringer Ingelheim GmbH

www.actilyse.com

Realisation

infill healthcare communication

www.infill.com

Supported by

Professors Peter Schellinger & Patrick Goldstein

Indications for IV rt-PA

Diagnosis of ischaemic stroke comfirmed clinically.

Time of ischaemic stroke less than 4.5hrs from onset

of stroke.

Consent obtained from patient/guardian.

Measurable and clinically significant deficit on NIHSS

scale examination (6-22)

CT brain scan does not show hemorrhage or non

vascular cause of stroke.

Patient‟s age >18 years, <80 years.Back

Absolute contra indications for IV rt-PA

Time of onset unknown or „ wake up‟ stroke.

Coma or severe obtundation with fixed eye deviation

and complete dense hemiplegia.

Only minor stroke deficit which appears to be rapidly

improving.

Seizure observed or known to have occurred at onset

of stroke.

Hypertension with systolic ≥ 180mmHg or diastolic

>110mmHg on repeated measurements.

Absolute contra indications for IV rt-PA -

cont

Clinical presentation suggestive of SAH even if CT

Brain scan is normal.

Presumed septic embolus.

Patient has received heparin within the last 48 hours

and has elevated PTT or has a known hereditary or

acquired haemorrhagic diathesis (PT or APTT greater

than normal)

INR > 1.7

Platlet count < 100 000/ul

Serum glucose < 2.8 mmol or >22 mmol/l

Relative contraindications for IV rt-PA -

Severe neurological impairment with NIHSS>22?

Age > 80 years.

CT Brain evidence of extensive MCA territory

infarction greater than 1/3 of MCA territory.

Stroke or serious head injury within the past 3 month

where the risk of bleeding outweight the benefit of

therapy.

Major surgery within the last 14 days.

Suspected recent (within 30 days) myocardial

infarction


Patient has known history of ICB , SAH, known

intracranial AVM or previously known intracranial

neoplasm such that, in the opinion of the clinician, the

increased risk of intracranial bleeding would outweigh

the potential benefits of treatment.

Recent (within 30 days) biopsy of a parenchymal

organ or surgery that, in the opinion of the

responsible clinician, would increase the risk of

unmanageable bleeding.

Recent (within 30 days) trauma with internal injuries

or ulcerative wounds.


GI or GU haemorrhage within the last 30 days or any

active or recent haemorrhage that, in the opinion of

the responsible clinician, would increase the risk of

unmanageable bleeding.

Arterial puncture at non compressible site within the

last 7 days.

Concomitant serious, advanced or terminal illness or

any other condition that in the opinion of the

responsible clinician would pose a risk to treatment

Back

Back

ACUTE ISCHEMIC STROKE

FLOW CHART / CHECK LIST

Total dose : 0.9mg/kg(<100mg)First dose:

10%of total dose given bolus over 10 minute.

Second dose :The remaining dose infused over 1

hour.Do not mix the drug with other drugs(dedicated IV line)

Dose & Administration

Step 1 : Bawa preskripsi wad ke Farmasi

Kecemasan.Sila pastikan dos ubat ditulisdan pastikan Doktor Pakar neurologiyang endorse ubat.

Example:IV Actilyse 7mg bolus over 1 minute followed by 63mg infusion over 1 hour

(Sila pastikan pegawai farmasi di kecemasan menulis dos ubat sekiranya dos tidak ditulis doktor) Berat pesakit diperlukan.Ingat!!

How to prepare the drug?

Step 2 : Confirm bolus dose and infusion

dose with Neurologist


Step 3 : Reconstitute using the solvent provided.

Use the transfer cannula provided. Only reconstitute after a written

prescription is done. After reconstitution, concentration is 1mg/ml.

Do not shake the vial. Just swirl it. Let solution to stand for a few minutes to clear large

bubbles Please take note that patient might need 2 vial..


Step 4 :Use 10ml syringe for withdrawing bolus dose.Eg : 7mg bolus stat. Jadi syringe out 7 ml.

Step 5 : Label Nama Ubat dan DosEg : IV Actilyse 7 mg(7ml)

Remember : bolus dose will be administered by the Dr for 1 minute.


Step 6 : Use 10ml syringe for withdrawing

10% of total dose ( bolus dose.)

Eg : 7mg bolus stat. Jadi syringe out 7 ml.


Step 7 : Use 1 or 2 50ml syringe for withdrawing

the dose for infusion.(Do NOT syringe out All the balance!)Cth: Jika Total dose :63mg(63ml)=2 vialDose bolus :6.3mg(6.3ml)Dose Infusion:63ml-6.3ml=56.7ml

The balance:

Disposed in sharp bin!!


Please label the infusion correctly

Eg. Label :• Concentration/dose on each syringe Nama ubat Masa start infusion Cth: 56.7ml continuos infusion 1 hour Syringe 1 :IV Actilyse 50mg Start:7am at 56.7ml/hr Syringe 2 :IV Actilyse 6.7 mg Start:? at 56.7ml/hr


ASPECT Score

C- Caudate,

I- Insularribbon,

IC- Internal Capsule,

L- Lentiform nucleus,

M1- Anterior MCAcortex, M2-

MCA cortex lateral to the

insular ribbon,

M3- Posterior MCA cortex,

M4, M5, M6 are the anterior,

lateral and posterior

MCAterritories immediately

superior to M1, M2 and M3,

rostral to basalganglia.

Subcortical structures are

allotted 3 points (C, L, and

IC).MCA cortex is allotted 7

points (insular cortex, M1, M2,

M3, M4, M5and M6)

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