HOW DO I DEAL WITH AN ACUTE STROKE

THE MALAYSIAN SOCIETY OF HYPERTENSION (MSH) 11th ANNUAL SCIENTIFIC MEETING

19th January 2014, 1430-1500

Ooi Phaik Yee

Neurologist

Hospital Sungai Buloh

STROKE : INTRODUCTION •  WHO 1970 definition

•  Rapidly developing clinical signs of focal (or global) disturbance of cerebral function, lasting > 24H or leading to death, with no apparent cause other than that of vascular origin

•  ischemic vs hemorrhagic

•  In the past, management strategy focused on •  Supportive care •  Prevention of complications •  20 prevention

WHAT IS CHANGING NOW?

THROMBOLYSIS FOR ISCHEMIC STROKE

WITHIN 4.5H

TIME IS BRAIN !!!!!!

Presentation of acute stroke within 4.5H

ABC IV-O2-monitor

§  Obtain time of onset §  vital signs §  NIHSS §  RBS

Iv D50% 50cc

Administer 1 of the following iv Labetolol 10 – 20mg

or iv nicardipine 5mg/H Non-contrasted CT brain

Recheck BP Do not give rtPA

rtPA 0.9 mg/kg Max 90mg

10% bolus over 1min Remainder infused over 1 H

Stop therapy

Admit to stroke unit

Frequent BP check No antiplatelet for 24 hours

No heparin for 24 hours Frequent neuro exams

KIV repeat CT bran

RBS< 2.7

BP>185/110

BP<185/110

ICH+

Clinically worsen

BP>185/110

PATHWAY FOR ACUTE STROKE MANAGEMENT

HISTORY: IMPORTANT INFO

•  Onset: •  if undefined, taken as “the last time patient was seen normal” •  ‘wake-up stroke”

•  Circumstances of stroke development (? Potential cause)

•  Comorbidities: CV risk factors & important PMHx

•  predisposition to bleeding complications

•  Exclude stroke mimics

•  Young pts: drug abuse, OCP, infection, migraine, trauma

FEATURES OF CLINICAL SITUATIONS MIMICKING STROKE

•  Psychogenic

•  Seizures

•  Hypoglycemia

•  Migraine with aura

•  Hypertensive encephalopathy

•  CNS abscess

•  CNS tumor

•  Drug toxicity

PHYSICAL EXAMINATION

•  Vital signs: BP, HR, SpO2, T

•  Head & neck: trauma

•  Neck: carotid bruits

•  CVS

•  Skin: coagulopathies, platelet disorders, signs of trauma, or embolic lesions

•  Standardized neuro examination: brief & thorough

NATIONAL INSTITUTES OF HEALTH STROKE SCALE (NIHSS)

•  objectively quantify the impairment of stroke •  11 items, each scoring between 0-4 •  0= normal function •  a higher score is indicative of some level of impairment •  Total score: 0-42

•  0 = no stroke •  1-4 = minor stroke •  5-15 = moderate stroke •  15-20 = moderate/ severe stroke •  21-42 = severe stroke

•  Score for thrombolysis: typically 4-24

INVESTIGATIONS

EVALUATION FOR SUSPECTED ACUTE STROKE

•  All patients •  Non-contrasted CT brain or MRI •  Blood glucose •  RP/ electrolytes •  FBC •  Markers for cardiac ischemia ( raised in

5-34%) •  PT/APTT •  ECG

•  Selected patients

•  TT or ECT if patient taking direct thrombin inhibitor or factor Xa inhibitor

•  LFT •  Toxicology •  Blood alcohol level •  Pregnancy test •  ABG ( hypoxia suspected) •  CXR (lung disease suspected) •  LP (SAH suspected) •  EEG ( seizure suspected) •  Genetic testing ( suspected genetic

disorders eg MELAS, CADASIL etc)

TIME IS BRAIN…..DO NOT DELAY

•  Blood glucose before rtPA : a must •  Baseline ECG & cardiac markers

•  Prolonged QTc, ST depression, T inversion ( particularly if involve insular cortex) in stroke

•  The rate of unsuspected coagulopathy & thrombocytopenia is low

•  CXR not always necessary (change management only in 3.8%)

•  do not wait for the normal lab results

URGENT NEUROIMAGING •  exclude bleed or non vascular cause •  NECT is generally sufficient •  For rtPA: Either NECT or MRI •  to be interpreted within 45min of arrival •  Selected pts

•  noninvasive intracranial vascular study: for IA -fibrinolysis or mechanical thrombectomy

•  CT perfusion & MRI perfusion + diffusion imaging: ‘wake-up stroke’

CHANGES ON NCECT

•  Early ( within few hours) : subtle loss of grey white matter differentiation, eg •  lenticular obscuration •  insular ribbon sign/ cortical ribbon sign •  sulcal effacement

•  Depends on infarct size, severity & onset

LENTICULAR OBSCURATION •  Normal CT brain

• 

•  •  • 

INSULAR RIBBON SIGN

Dense MCA sign MCA dot sign

MRI-DWI

•  Preferred as 1st line if available

•  DWI has a high sensitivity (88% to 100%) & specificity (95% to 100%)

•  Rapid detection of within minutes

•  allows identification of the lesion size, site, & age

•  can detect relatively small cortical lesions or subcortical lesions in brainstem or cerebellum

•  Comparison of diffusion-weighted MRI & CT in acute stroke, Lansberg, et al, Neurology April 25, 2000 vol. 54 no. 8 1557-1561

Perfusion study: A middle age man with left hemiparesis

Latchaw R E et al. Stroke. 2003;34:1084-1104

Copyright © American Heart Association, Inc. All rights reserved.

ONCE ISCHEMIC STROKE ESTABLISHED……

Thrombolysis

MECHANISM OF ACTION

INTRAVENOUS THROMBOLYSIS •  Approved by US FDA in 1996

•  2-part NINDS rtPA Stroke Trial •  624 patients with ischemic stroke, placebo or intravenous rtPA within 3H of

symptom onset

•  rtPA : favorable outcome (OR, 1.9; 95% CI, 1.2–2.9)

•  Excellent outcomes on individual functional measures: rtPA vs placebo •  global disability : 40% versus 28% •  global outcome : 43% versus 32% •  ADL : 53% versus 38% •  neurological deficits : 34% versus 20%

COCHRANE META-ANALYSIS

•  Conclusion from 21 completed RCTs •  Substantial benefit if given within the first 3H •  Moderate net benefit if given within 3-4.5H •  Moderate net benefits if Intra-arterial fibrinolytic therapy given in the 3-6H

window

•  In May 2009, the AHA/ASA guidelines expands the window of treatment from 3H to 4.5H

INDICATIONS & CONTRAINDICATIONS FOR THROMBOLYSIS

INCLUSION CRITERIA FOR IV RTPA WITHIN 3H

•  Diagnosis of ischemic stroke causing measurable neurological deficit

•  Onset of symptoms <3H before beginning treatment

•  Age ≥18yo

CONTRAINDICATIONS (RTPA WITHIN 3H)

•  Contraindications •  Significant head trauma or prior stroke

in previous 3 months •  Symptoms suggest SAH •  Arterial puncture at non-compressible

site in previous 7 days •  Hx of previous ICH •  Intracranial neoplasm, AVM or

aneurysm •  Recent intracranial or intra-spinal

surgery •  Elevated BP (SBP>185,

DBP>110mmHg) •  Active internal bleeding •  Blood glucose <50mg/dl (2.7mmol/L) •  CT demonstrates multilobar infaction

(hypodensity >1/3 cerebral hemisphere)

•  Acute bleeding diathesis, including but not limited to :

•  platelet<100, heparin received within 48H, resulting in abnormal elevated aPTT> upper limit of normal, current use of anticoagulatn with INR>1.7 or PT> 15s, current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated sensitive lab test ( eg aPTT, INR, platelet, ECT, TT or appropriate factor X activity assay

Relative contraindications •  Only minor or rapidly improving stroke

symptoms ( clearing spontaneously) •  Pregnancy •  Seizure at onset with post-ictal

residual neurological impairments •  Major surgery or serious trauma within

previous 14 days •  Recent GI or urinary tract

hemorrhage ( within previous 21 days) •  Recent AMI ( within previous 3

months)

ADDITIONAL INCLUSION & EXCLUSION: IV RTPA WITHIN 3-4.5 H

•  Inclusion criteria

•  Dx of ischemic stroke causing measurable neurological deficit •  Onset of symptoms within 3-4.5H before beginning treatment

•  Relative exclusion criteria •  Aged >80 years •  Severe stroke (NIHSS>25) •  Taking an oral anticoagulant regardless of INR •  Hx of both diabetes & prior ischemic stroke

INTRAVENOUS ADMINISTRATION OF RTPA

•  Infuse 0.9 mg/kg (maximum dose 90 mg) over 60 minutes, with 10% of the dose given as a bolus over 1 minute.

•  Careful monitoring: •  intensive care or stroke unit •  Careful monitoring & stabilization of BP (keep <180/105mmHg) •  If suspicion of ICH, to stop rtPA & obtain urgent CT brain

BENEFITS OF THROMBOLYSIS

•  90min : 2.6 fold

•  91-180min : 1.6 fold

•  181-270min : 1.3 fold

•  271-360min : no statistically significant good outcome

•  Source: Strokeeducation.co.uk

ED BASED CARE: GOALS FOR TIME FRAME

•  Door to physician <10 mins

•  Door to stroke team <15 mins

•  Door to CT initiation <25 mins

•  Door to CT interpretation <45 mins

•  Door to drug (80% compliance) <60 mins

•  Door to stroke unit admission <3 hours

•  Source: Bock

INTRA-ARTERIAL RTPA

•  In carefully selected patients <6H duration

•  MCA occlusions, who are not otherwise candidates for iv rtPA

•  optimal dose is not well established

•  rtPA does not have FDA approval for intra-arterial use

•  higher recanalization rates, less systemic side effects

•  off-label therapy for stroke at tertiary centers •  within 6H in anterior circulation •  up to 12-24H in posterior circulation

•  ICH rate for intra-arterial thrombolysis: 10% (6% in intravenous)

PUBLIC HOSPITALS THAT OFFER THROMBOLYSIS SERVICE IN MALAYSIA

•  UMMC

•  HUKM

•  HUSM

•  Kuala Lumpur General Hospital

•  Hospital Sultanah Nur Zahirah, Kuala Terengganu

•  Hospital Seberang Jaya

•  Hospital Raja Permaisuri Bainun, Ipoh

•  Sarawak General Hospital

GENERAL SUPPORT CARE & TREATMENT OF ACUTE COMPLICATIONS

AIRWAY, VENTILATOR SUPPORT & SUPPLEMENTAL OXYGENATION

•  Hypoxia •  63% has hypoxia (SpO2 <96% for >5 min) within 48 hours of stroke onset •  All pts with cardiac or pulmonary disease have hypoxemia.

•  Causes: partial airway obstruction, hypoventilation, aspiration, atelectasis, & pneumonia.

•  Higher risk in pts with decreased consciousness or brain stem dysfunction

•  careful observation & prevention

•  Early intubation may be needed

•  maintain oxygen saturation >94%

PATIENT POSITIONING & MONITORING

•  can influence oxygen saturation, cerebral perfusion pressure, MCA mean flow velocity & ICP

•  If non-hypoxic= supine

•  If at risk for airway obstruction/aspiration, elevated ICP= head up 15-30 degree

HYPERTHERMIA

•  1/3 has hyperthermia (T> 37.6) in the first hours of stroke

•  Ass w poor neurological, increased short term mortality

•  Maintain normothermia & reduce the acute rise in temperature

•  Look for the cause

BLOOD PRESSURE

•  Elevated BP is common after stroke

•  often higher in preexisting HPT

•  Mild hypertension is desirable at 160-180/90-100 mmHg

•  moderate arterial HPT might be •  advantageous (improving cerebral perfusion), or •  detrimental (exacerbating edema & hemorrhagic transformation)

•  Extreme arterial HPT is clearly detrimental

•  Rx is individualized

IN GENERAL…..

•  For ischemic stroke •  not to lower BP in 1st 24H unless BP >220/120 mm Hg or •  concomitant specific medical condition that requires BP lowering

•  myocardial ischemia, aortic dissection, & heart failure

•  Can initially lower SBP by 15% & monitor for neurological deterioration •  In thrombolysis, BP must be always maintained below 180/105 mm Hg

•  For hemorrhagic stroke •  Rx for HPT is more aggressive •  Maintain MAP<130 mm Hg if pre-existing hypertension •  In raised ICP , CPP(MAP–ICP) should be kept >70 mm Hg •  If SBP falls below 90 mm Hg, pressors should be given

ARTERIAL HYPOTENSION

•  BP lower than premorbid BP

•  Ass w poor outcome in multiple studies

•  suggests another cause than stroke •  cardiac arrhythmia/ischemia, aortic dissection, or shock

•  Needs urgent evaluation, diagnosis & correction

•  May need vasopressor

INTRAVENOUS FLUIDS

•  Extreme hypovolemia & hypervolemia are harmful

•  Maintenance iv fluids for euvolemic pts

•  If hypovolemic, replace the deficit followed by maintenance

•  Modified protocol in special condition eg SIADH, fever

•  for acute ischemic stroke, use isotonic solutions such as 0.9% saline

GLUCOSE CONTROL

•  Hypoglycemia: stroke mimics & cause seizure

•  American Diabetes Association recommendation: •  maintain the blood glucose140 to 180 mg/dL (7.8-10mmol/L)

•  Maintain blood glucose 4-11 mmol/L (NICE)

•  persistent hyperglycemia in the first 24H after stroke: poor outcomes

USE OF ANTICOAGULATION IN STROKE

•  increased risk of bleeding with early administration of either UFH or LMWH

•  does not lower the risk of early recurrent stroke or neurological worsening

•  Data are insufficient in intracardiac or intra-arterial thrombi.

•  The effectiveness of urgent anticoagulation is not established for arterial dissection or vertebrobasilar disease

•  The timing of initiation after stroke have not been established

ANTIPLATELETS

•  Oral aspirin (initial dose is 325 mg) within 24 to 48H is recommended for treatment of most ischemic stroke patients

•  Aspirin should be continued in the presence of asymptomatic ischemic stroke w hemorrhagic transformation.

•  Role of clopidogrel for acute ischemic stroke is not well established

OTHER ASPECTS

•  comprehensive specialized stroke care (stroke units) is recommended •  reduce mortality & long-term dependency

•  Treat pneumonia or UTIs with appropriate antibiotics

•  Routine indwelling bladder catheterization is not recommended

•  DVT prophylaxis •  Subcutaneous anticoagulants •  Compression stocking

•  Early mobilization

•  Early referral for rehabilitation

•  Swallowing impairment •  increased risk of aspiration & death •  A preserved gag reflex may not indicate safety with swallowing

•  Swallowing assessment (bedside assessment or formal referral to speech therapist)

•  If failed swallowing test, for NG tube feeding until 2 to 3 weeks before deciding for PEG

BRAIN EDEMA & SURGERY

•  major infarctions: higher risk for brain edema & increased ICP

•  Involvement of uncus of temporal lobe: rapid herniation

•  Cytotoxic edema typically peaks on D3-D4, though malignant edema may occur in 1st 24H

•  close monitoring during the first few days

•  transfer to institution with neurosurgical expertise should be considered

NEUROSURGICAL REFERRAL (NICE)

•  Should be referred within 24H, treated within 48H

•  Criteria •  Age ≤60 •  MCA territory infarct w NIHSS>15 •  Decreased level of consciousness to give a score of 1 or more on item 1a NIHSS •  Infarct >50% of MCA territory on CT, with or without additional ACA or PCA

territory involvement, or infarct volume> 145cm3 on MRI DWI

•  mean mortality rate •  Decompression: 20 to 30% (range 8-50%) •  Conservative: 70 to 80%

•  better outcome if performed early before signs & symptoms of herniation

OTHERS

•  corticosteroids are not recommended for cerebral edema & increased ICP

•  Recurrent seizures after stroke should be treated

•  Prophylactic use of anticonvulsants is not recommended

CONCLUSION •  With availability of thrombolytic therapy, acute ischemic stroke

management would revolutionize from conservative approach to aggressive revascularization within the recommended therapeutic window.

•  The general management of acute stroke is aimed to stabilize patient, treat acute complications & enhance recovery.

•  Multidisciplinary care is important to deliver good stroke care

•  stroke unit care should be widely implemented whenever & wherever possible

THANK YOU •  References

•  Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/ American Stroke Association, Stroke. 2013;44:870-947

•  Stroke: diagnosis & initial management of acute stroke & transient ischemic attack, national institute for health & clinical excellence (NICE), July 2008

•  Management of ischemic stroke, 2nd edition, Malaysian clinical practice guidelines 2012

•  Ischemic stroke & transient ischemic attack, EFNS guideline 2011 •  Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A

Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association, Stroke. 1999;30:905-915