ER Resident Orientation

Jana Wold, MD

Stroke Fellow, Dept. of Neurology

University of Utah

Who are we:

• We are a Joint Commission/AHA certified primary stroke center committed to providing comprehensive, high quality care for patients with cerebrovascular disease.

• We are dedicated to the advancement of innovative stroke research in areas of prevention, imaging, treatment, genetics, epidemiology, and quality.

Stroke Center Staff

Stroke:

3rd most common cause of death in US >700,000 strokes per year 1 stroke in US every 45 secs 1 death from stroke every 3 mins

No. 1 cause of adult disability Cost: $58 billion (medical, rehab, employment)

due to stroke in 2006

Emergent Stroke Care and the Chain of Survival

Patient Calling EMS ED Stroke Hospital Knowledge 911 System Staff Team Unit

Stroke is a progressive injury to an area of brain starved of

nutrients and oxygen

Cerebral Embolism CardiacvalvularAtrial fibrillationMILeft atrial myxomacardiomyopathy

Paradoxicalpulmonary AVMatrial/ventricular shunts (PFO)pulmonary vein thrombosispulmonary tumors

Artery to Artery embolismcholesterolatheromacomplications from neck surgerycarotid thrombusemboli distal to unruptured aneurysmfat or air embolism

Large Artery Distribution Stroke

• Anterior Cerebral

• Middle Cerebral– dominant– nondominant

• Posterior Cerebral

• Vertebrobasilar

Lacunar Stroke

Small Vessel Disease Pathology: Lipohyalinosis

Risks: HTN, DM. tobacco

Other mechanisms

Watershed Infarct=

Loss of flow usually across a vessel stenosis infarction in areas bordering two vascular

territories

But what if the symptoms have resolved???

Definition of TIA

• Traditional: focal neurological symptoms lasting less than 24 hours– Limitations:

• Not physiologic• Up to one third of TIA if scanned within 6 hours of onset

even if clinically resolved will be positive of MRI diffusion-weighted imaging

• New: focal neurological symptoms secondary to interruption of blood flow to the brain or retina lasting between 10-30 minutes and completely resolving

Prognosis of TIA

• Johnston, et al., JAMA 2000;284:2901-6– Retrospective cohort study of Kaiser-

Permanente data base– 1707 pts. with ED diagnosis of TIA– Follow-up for 90 days: risk of stroke, other

events including death, recurrent TIA, hospitalization for cardiovascular events

Prognosis of TIA

• 180 pts. (10.5%) returned to ED with stroke w/i 90 days

• 91 of those (5.3%) returned with stroke in the first 2 days

• Factors associated with stroke:– Age >60 years, diabetes, symptom duration

longer than 10 minutes, weakness, speech impairment

Short-term Prognosis after Emergency Department Diagnosis of TIA

Johnston SC, et al. JAMA 2000;284:2901-2906.

10.5%

12.7%

2.6% 2.6%

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

Stroke RecurrentTIA

CV event Death

Outcome events Inclusion criteria:

Objective:

Outcome measures:

Total events:

TIA by ED physicians

Short-term risk of strokeafter ED diagnosis

Risk of stroke and otherevents during the 90 daysafter index TIA

25.1%

Within48 hr

Within90 days

5.3%

Population-based study of risk and predictors of stroke in the first few hours after a TIA.

• About half of all recurrent strokes during the 7 day period following a

TIA occur in the first 24 hours.

Chandratheva A, Mehta Z, Geraghty OC, Marquardt L, Rothwell PM; Oxford Vascular Study.

Neurology. 2009 Jun 2;72(22):1941-7.

ABCD Features Predictive of Seven-Day Risk of Stroke in Patients With

Probable or Definite TIA• A = Age ≥60 years (1 point)• B = Blood pressure (SBP >140 and/or DBP

≥90 mm Hg; 1 point)• C = Clinical features (unilateral weakness,

2 points; speech disturbance without weakness, 1 point)

• D = Duration of symptoms (≥60 minutes, 2 points; 10-59 minutes; 1 point)

Rothwell PM, et al. Lancet. 2005;366:29-36.

Oxford ABCD Score

• Significantly predictive of 7-day risk of stroke in a cohort of 190 TIA patients

• 95% of strokes (19 of 20) occurred in patients with a score of 5 or greater

• 7-day risk was:

– 0.4% with a score less than 5

– 12% with a score of 5

– 31% with a score of 6Rothwell PM, Giles MF, Flossmann E, et al. A simple score (ABCD) to identify individuals at high early risk of stroke after transient ischaemic attack. Lancet 2005;366(9479):29-36

Seven-Day Risk of Stroke Stratified According to ABCD Score

10.5 (6.2-14.9)20 (100%)188 (100%)Total

35.5 (18.6-52.3)11 (55%)31 (16%)6

16.3 (6.0-26.7)8 (40%)49 (26%)5

2.2 (0-6.4)1 (5%)46 (24%)4

0032 (17%)3

0028 (15%)2

002 (1%)≤1

Risk (95% Cl)Strokes (%)Patients (%)ABCD Score

Seven-day risk of stroke stratified according to ABCD score at first assessment in the OXVASC validation cohort of patients with probable or definite TIA. Rothwell PM, et al. Lancet. 2005;366:29-36.

What is the most appropriate work-up?

Differential DiagnosisTransient Neurological Symptoms

• TIA

• Seizure

• Migraine

• Metabolic (hypoglycemia)

• Multiple sclerosis

• Radiculopathy, myelopathy

or neuropathy

What if the symptoms are NOT going away???

Call a Brain Attack!!

Brain Attack Team

• ER attending and resident• Brain Attack Attending• Stroke Fellow• Neurology Resident• Interventional Radiologists• Pharmacists• Lab Tech• ECG Tech• CT/MRI Techs

Brain Attack Attendings

• Dr. Elaine Skalabrin

• Dr. Jennifer Majersik

• Dr. David Renner

• Dr. Dana DeWitt

• Dr. Holly Ledyard

• Dr. Jeff Wagner

• Dr. Byron Spencer

What is my role?

• ER Doc does:

• ABCs• Airway• Breathing• Circulation• Skin Signs• Pupils

• ER Staff does:

• Vitals• Labs• IV (need 18 gauge for

CT)• Labs• ECG• Weight

What’s important?

• Last time seen normal

• Time symptoms began

• Medication list (are they on Coumadin)

• Any recent surgery

• Two part study– First part: to assess whether tPA would result in

early neurologic improvement (w/i 24 hrs) defined as complete resolution of symptoms or improvement of 4 pts on NIHSS

– Second part: to assess if their would be a sustained improvement in tPA vs. placebo arm at 3 months

Tissue plasminogen activator for acute ischemic stroke

• Inclusion criteria:– Ischemic stroke with clearly defined

onset– Measurable deficits on NIHSS– CT without hemorrhage

• Exclusion criteria:– Same as current exclusions

• Part 1: 291 pts• Part 2: 333 pts

tPA Exclusion Criteria1. Minor Symptoms2. Seizure at onset3. Stroke/head trauma w/n 6 mo’s4. Major surgery w/n 14 days5. Known h/o intracranial hemorrhage, AVM, intracranial neoplasm or

aneurysm6. Sustained SBP>185 mm Hg or DBP>110 mm Hg7. Elevated BP that requires continuous IV tx8. Symptoms suggestive of SAH9. GI or urinary tract hemorrhage w/n 21 days10. Arterial puncture or lumbar puncture at noncompressible site w/n 7 days11. Received heparin w/n 48 hrs and had elevated PTT12. PT>15 sec or INR>1.713. Plts<100,000mL14. Serum glu<50mg/dL15. MI w/n 3 mo’s16. Active bleed17. Neurological symptoms cleared spontaneously

Tissue plasminogen activator for acute ischemic stroke

Outcomes based upon stroke type

Intracranial Hemorrhage

Two variables associated with increased risk of ICH:

- severity of NIHSS

- brain edema or mass effect on CT

Is rt-PA efficacious in the treatment of acute ischemic

stroke?

YESBenefits > risks

Reduces all degrees of disability

No increase in mortality

Confirmed in randomized controlled trials

FDA approval in 1996

Early treatment associated with better outcome

0

1

2

3

4

5

6

7

8

60 70 80 90 100 110 120 130 140 150 160 170 180

Minutes form Stroke Onset to Treatment

Od

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Rati

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ECASS III

• Double blind, parallel group trial• tPA given at 3 - 4.5 hrs• Inclusion:

– Age 18-80– Acute stroke– Negative CT for hemorrhage– No neurologic improvement, symptoms for at least 30

minutes• Exclusion:

– NIHSS>25 “severe stroke”– Combined DM and prior stroke

ECASS III• Primary end

point:– mRS at 90 days

• 821 pts enrolled• Significantly more

favorable outcomes with tPA

• More hemorrhages with tPA, but mortality the same

Management after thrombolytics

• Assess for changes in neurological status• Blood pressure monitoring• Assess for bleeding complications• Monitor use of other medications• Frequent vital signs and neurological

checks…– q 15 min for the first 2 hours – q 30 min for the next 6 hours– Q hr for 16 hours

Post-TPA blood Pressure Guidelines

• Goal is <180/105

• If BP >180/105 on 2 readings 5 minutes apart– Labetalol or hydralazine

• BP >230/140– Labetalol as above or Nicardipine drip

• Diastolic BP > 140– Consider Nitroprusside or Nicardipine drip

What if they have a clot in a large vessel visible on CT?

Intra-arterial Thrombolysis

• PROACT II: clinical efficacy trial– Randomized, open-label design with blinded follow-up– Pt selection the same, but excluded pts with early

signs of infarction >1/3 MCA territory– Pts received 9mg r-proUK + heparin vs. IV heparin– All received low-dose heparin

– Primary outcome: mRS 2 or less at 90 days

• 180 pts – median NIHSS 17

PROACT II

• Clinically and statistically significant benefit in the treated group

• 15% absolute risk reduction (slight or no disability at 90 days) in the r-proUK group

• Symptomatic hemorrhage 10% r-proUK vs. 2% controls– But, no excess mortality (24% vs. 27%)

• 7 pts with an MCA occlusion would require IAT for 1 of them to benefit

• Prospective, single arm, multicenter trial

• Eligibility:

• >18 yrs old

• stroke symptom duration between 3-8 hrs or between 0-3 hrs and contraindication for IV tPA

• NIHSS>8

• CT without hemorrhage

• Occlusion of a treatable vessel = intracranial vertebral, intracranial ICA, ICA terminal bifurcation, MI branch of MCA

• In part II, M2 branch allowed

MERCI trial

• 151 pts

• IA thrombolytics were allowed in cases of treatment failure with the device and for distal embolus – 17 cases where IA tPA was used b/c the

device could not get the clot• These cases were not included as successes

• Median NIHSS was 19

MERCI

• Recanalization in 46%• Better than 18% spontaneous

recanalization rate seen in placebo group in PROACT II

• Therefore, FDA cleared the device for “restoration of blood flow in acute stroke patients who are otherwise ineligible for IV tPA, or in whom IV tPA has failed”– Not for treatment of stroke

CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients

with acute ischaemic stroke• 21,106 pts with acute ischemic stroke in

China

• ASA 160mg vs. placebo for 4 wks, given w/n 24 hrs of onset

• Primary end point:– Death from any cause w/i 4 wks– Death/dependence at discharge

• 21,106 pts enrolledLancet 1997; 349: 1641-49

CAST

• Statistically significant reduction in odds of death in the ASA group– Absolute difference of 5.4 fewer deaths/1000

pts

• Primary outcome of death/dependant at discharge– Non-significant trend favoring ASA

CAST and IST combined data

• ASA significantly reduced recurrent stroke risk (7 per 1000)

• For every 1000 acute strokes treated with ASA, about 9 deaths or nonfatal strokes will be prevented in the first few weeks

• 13 fewer pts will be dead or dependent at 6 months

TAKE HOMES

• A TIA is an Emergency!

• It is never wrong to call a brain attack

• Patients can always get follow-up in the Stroke clinic