By

Mohammad Binhussein

&

Ahmad Abolaban

General Supportive Care and Treatment of Acute Complications

1. ABC:

-Oxygen mask with a target oxygen saturation level 92%

-endotracheal tube should be placed if the airway is threatened (e.g. decreased

consciousness, who have bulbar dysfunction or GCS<8 )

General Supportive Care and Treatment of Acute Complications

1. ABC:

Nonhypoxic patients with acute ischemic stroke do not need supplemental

oxygen therapy (Class III, Level of Evidence B) (5)

General Supportive Care and Treatment of Acute Complications

• Hyperbaric oxygen ??

used to treat patients with ischemic neurological symptoms secondary to air embolism or caisson disease (5)

A systematic review found no evidence that hyperbaric oxygen improved outcomes after stroke or brain injury (5)

General Supportive Care and Treatment of Acute Complications

• Temperature :

(hyperthermia increases ischaemic neuronal injury)

sources of infection (pneumonia or urinary tract) should be treated with antibiotics, fever should be treated and antipyretic medications should be administered to lower temperature in febrile patients with stroke (5)

General Supportive Care and Treatment of Acute Complications

• Arterial hypertension :

lowering BPs may cause under perfusion of ischaemic penumbra

General Supportive Care and Treatment of Acute Complications

• Arterial hypertension :

Only Patients who have other medical

indications for aggressive treatment of blood pressure should be treated e.g. AMI

General Supportive Care and Treatment of Acute Complications

• Arterial hypertension :

medications should be withheld unless the systolic blood pressure is >220 mm Hg or the diastolic blood pressure is >120 mm Hg (5)

A reasonable goal would be to lower blood pressure by 15% during first 24

hours after onset of stroke (5)

General Supportive Care and Treatment of Acute Complications

• Arterial hypotension :

In exceptional cases, a physician may prescribe vasopressors to improve cerebral blood flow. If drug-induced hypertension is used, close neurological and cardiac monitoring is recommended (5)

Causes include: 1-Hypovolemia 2-Cardiac arrhytmias decrese cardiac out put

General Supportive Care and Treatment of Acute Complications

• Hyperglycemia and hypoglycemia

• Hydration

Dehydration is a potential cause of deep vein thrombosis (5) gives 50ml/hr’s NS.

General Supportive Care and Treatment of Acute Complications

• Nutrition :

An assessment of the ability to swallow is important before the patient is allowed to eat or drink

Patients who cannot take food and fluids orally should receive nasogastric, nasoduodenal, or PEG feedings to maintain hydration and nutrition (5)

General Supportive Care and Treatment of Acute Complications

• Nutrition :

Early vs. delayrd enteral feeding for stroke patient with dysphagia ??

Food study included two randomized trials that answer this question and shows that : early feeding with enteral nutrition does not appear to improve outcomes . And the 5% increase in survival was offset by an increase in pt. with extremely poor functional outcomes (i.e. bedridden state or needs assistance with walking and bodily needs) (6)

General Supportive Care and Treatment of Acute Complications

• Activity :

Aspiration precaution , head of the bed elevation to 308 physical therapy (3) & Early mobilization of less severely affected patients (5)

Subcutaneous administration of anticoagulants is recommended for treatment of immobilized

patients to prevent deep vein thrombosis

General Supportive Care and Treatment of Acute Complications

• Activity :

The use of intermittent external compression devices is recommended for treatment of patients who cannot receive anticoagulants (5)

Acute stroke treatment

Aim :

• 1- restore perfusion to ischemic tissue(Thrombolytic agent)

• 2- limit the ischemic cascade of biochemical events

(Neuroprotective agent)

Ischaemic Penumbra (3)

• Acute occlusion causes heterogeneous regions of ischaemia.

• Local flow depends on major arterial source and any collateral.

• Region without flow is the CORE

• Cells die within minutes.• Marginal perfusion =

PENUMBRA.• Tissue can remain viable for

hours.• Therapies targeted to

protecting these tissues.

Acute stroke treatment

• Thrombolytic agent:

used within 3 hours from the onset of ischemic stroke

Approved as a result of trial that use rt-PA on 625 patient and show 11% absolute increase in number of pt. with no or little deficits compared to placebo . (1)

NINDS

Acute stroke treatment

• Thrombolitic agent:

Three trials (ECASS, ECASS ll and ATLANTIS) shows no benefit of IV rt-PA over placebo if received after 3 hr’s. (1)

And shows higher incidence of parenchymal hemorrhage (19.8% vs 6.5% in ECASS) and (7% vs 1.1% in ATLANTIS study) . (1)

Acute stroke treatment

• And also confirm the clinical benefit of rt-PA shown in the NINDS trial.

• So, strict adherence to the guide line is essential for safety of patient.

• But only a small fraction of patients meet the NINDS criteria

• The new drug ( Desmoteplase ) in a trial shows a promising theraputic option.

Caution

• The use of anticoagulants and antiplatelet agents should be delayed for 24 hours after treatment

• potential side effect of angioedema that may cause partial airway obstruction

Careful

systolic blood pressure is ≤185 mm Hg and their diastolic blood pressure is ≤ 110 mm Hg and

maintained below 180/105 mm Hg for at least the first 24 hours (5)

Prognosis post Thrombolysis.Neurological deficit:

post tPA : 30 % normal or minimal neurological problems.

30% mild to moderate deficit

20% moderate to severe problems

20 % mortality

Functional disability:

3/12 post tPA : 50% with complete or almost complete independent functioning.

15% moderate dependence

15% complete dependence

20% mortality

Use of Streptokinase- MAST I, MAST E, ASK –increased mortality rate and ICH occurrence

So the rt-PA is the only thrombolytic approved by FDA

Acute stroke treatment

• Neuroprotective agent

Free radical trapping agent NXY059,Cerovive

Reduce the rate of symptomatic bleeding among patients given rtPA

At present, no intervention with neuroprotective actions has been established as effective in improving outcomes after stroke, and therefore none currently can be recommended. (5)

Ischaemic Cascade.• Processes occurring at cellular level• Happens within seconds to minutes of loss of glucose and oxygen

delivery to neurons.• Begins with loss of cellular electro- phsyiological function.• Cell metabolism changes: Aerobic Anaerobic

Depletion of ATP storesMembrane Ion pumps failIncreased intracellular Na, Ca .Ca mediated cytotoxic reactionRelease of excitatory neurotrans

(glutamate)Protease, Endonuclease, Phospholipase, NO synthase activation= free

radicals. Neuronal, Glial injury, plus oedema.

Anticoagulants in Stroke.• Heparin prevents recurrent cardioembolic strokes• No evidence it reduces brain injury in acute ischaemic

stroke• Risk of haemorrhagic transformation – some advocate

only after 48hrs.• Low molecular weight Heparin as prophylaxis of DVT.

Anticoagulants in Stroke.

• Anticoagulants :

- Does IV heparin prevent stroke progression or recurrence. (Is it effective/safe) ??

anticoagulant therapy vs. control acute ischemic stroke (4)

• A systematic review of twenty-two trials involving 23,547 patients. The anticoagulants tested were standard (heparin, LMWH, heparinoids, oral anticoagulants, and thrombin inhibitors) and the major findings:

• Based upon nine trials (22,570 patients), anticoagulant therapy didn’t reduce the no. of death from all causes .

• Based upon six trials (21,966 patients), anticoagulants didn’t reduce the no. of being dead or dependent at the end of follow-up .

• anticoagulant therapy associated with

-9/1000 fewer recurrent ischemic strokes.

-9/1000 increase in symptomatic intracranial hemorrhages.

-avoided 4/1000 pulmonary emboli. -9/1000 major extracranial hemorrhages.

Conclusion • not recommend full-dose anticoagulation for

treatment of unselected patients with ischemic stroke .

• Early anticoagulation may be given if stroke due to cardioembolism (significant valvular disease, severe congestive heart failure, or mechanical heart valves), large artery atherosclerotic stenosis with documented intraluminal thrombus, dissection of a cervical or intracranial large artery, and progressing stroke. (4)

Conclusion

• given after a brain imaging study has excluded hemorrhage and estimated the size of the infarct

• contraindications to anticoagulation large infarction, uncontrolled hypertension, or other bleeding conditions.

• Aspirin, clopidogrel, ticlopidine & dipyridamole are effective and safe therapy in reducing atherothrombotic stroke .

Selection of Antithrombotic Therapy for Ischemic Stroke Secondary Prevention

Antiplatelet Therapy• ASA

• Clopidogrel (Plavix)

• Dipyridamole + ASA (Aggrenox)

Two major clinical trials studied the benefits and risks of aspirin in the setting of acute ischemic stroke

the IST and CAST trials demonstrated that aspirin therapy in acute ischemic stroke led to 9/1000 decrease in the

nonfatal strokes and deaths if started within 48 hours (4)

initial dose 325 mg, thereafter 160 to 325 mg/day (4),(5)

Aspirin ClopidogrelVS

Based on existing data no clear indication to prescribe clopidogrel over aspirin for prevention of recurrent atherothrombotic stroke unless pt. is aspirn-intolerance (1)

CAPRIE trial

Combination of Antiplatelet

Heart Center Online , http://www.heartcenteronline.com

1. Aspirin and dipyridamole

2. Aspirin and clopidogrel ? MATCH trial: ASA 75mg + Plavix 75mg vs.Plavix 75mg

Endothelial Damage

Dipyridamole

Platelet adhesion

TXA2/ADP Gpllb/llla expression

Aspirine

Study Discussed in 17th European Stroke Conference, Nice, France, May 14, 2008

The beneficial effects of aspirin and dipyridamole for secondary stroke prevention appear to be additive . the combination of aspirin and extended-release dipyridamole (ER-DP) is twice as effective as aspirin alone for stroke prevention after 2 year (1) , (2)

the combination does not provide additional benefit or risk over aspirin alone for MI. (2)

The most adverse effect was headache (39.2%) . (1)

PRoFESS trial

Aspirin & Clopidogrel

• Benefit vs. Risk (12562 patient)– Rate of recurrent stroke is the 1.2% in clopidogrel-aspirin

group compared with 1.4% with aspirin-alone . (1)– rate of major bleeding in the clopidogrel-aspirin group

3.7% vs. 2.7% with aspirin-alone group. (1)– Rate of minor bleeding were twice in clopidogrel-aspirin

group compared with aspirin-alone group ( 5.1% vs. 2.4% ). (1)

Aspirin & Clopidogrel

• Benefit vs. Risk (7599 patients)

Overall, treatment with aspirin and clopidogrel compared with clopidogrel alone might prevent 10 ischemic events per 1000 treated (not statistically significant) at the cost of 13 life-threatening hemorrhages per 1000 treated

MATCH trial

Therapeutic approach to Stroke.• 4 phases : a)preventative measures in general

b)supportative and medical mx in acute phase

c)measures to mitigate the pathologic or atherothrombotic process.

d)rehabilitative and physical therapy programmes in post stroke period.

Therefore, classes of drugs used : Neuro protectants

Anticoagulants

Thrombolytics.

Thrombolysis :Where are we now ? • Collective results from trials show consistent pattern of

results.• Tx within 3 hours benefit substantially• Within 3 to 6 hrs : modest benefit, but increased risk of

bleed.• Intra arterial thrombolysis with pro Urokinase (PROACT II)

1999, good functional outcome after 90 days.• January 2003 :Actilyse launched as first and only tx for acute

ischaemic stroke.• Only used in units registered with SITS-MOST – all patients

treated form part of database.• Patients must be within 3 to 4 hrs of event.

The problems with Thrombolysis.Exclusion criteria: Stroke or serious HI in last 3

months Major surgery or body trauma

in last 2 weeks. Prior ICH Intra cranial Neoplasm AV malformation or Aneurysm GI haem in last 21 days Arterial puncture at non

compressible site or LP in last week.

Oral anticoag, with INR >1.7

Complications: Intracerebral Haemmorhage

NINDS trial 6.4% with tPA (24-36hrs)

Signals= raised BP, headache, decreased neuro func, vomiting.

Oozing from IV puncture sites (30% of cases).

Angioedema (rare)

The Perceptions of StrokeThe Perceptions of StrokeMYTH

• Stroke is not preventable

• Stroke cannot be treated

• Stroke only strikes the elderly

• Stroke happens in the heart

• Stroke recovery ends after 6 months

REALITY• Up to 80% percent of strokes

are preventable• Stroke requires emergency

treatment

• Anyone can have a stroke

• Stroke is a “Brain Attack”

• Stroke recovery can last a lifetime

Summary

Summary.• Treatment options for Acute

stroke have progressed rapidly over last 10 years.

• New therapeutic options will be available in the near future.

• Measures in the Emergency Department can influence outcome and recovery.

• The overall incidence of Stroke can only increase as population age increases.

Reference.1. Antithrombotic and Thorombotic Therapy for Ischemic

Stroke ( Oriana Cornett, Lenore C. Ocava, Manjeet Singh, Samit Malhotra, Daniel M. Rosenbaum) literature review

2. Up To Date : Antiplatelet therapy for secondary prevention of stroke, literature review for version 16.2

3. emedicine.com/neuro/topic9.htm

4. Up To Date : Antithrombotic treatment of acute ischemic stroke, literature review for version 16.2

5. A Guideline From the American Heart Association/ American Stroke Association 2007

Reference.1. Antithrombotic and Thorombotic Therapy for Ischemic

Stroke ( Oriana Cornett, Lenore C. Ocava, Manjeet Singh, Samit Malhotra, Daniel M. Rosenbaum) literature review

2. Up To Date : Antiplatelet therapy for secondary prevention of stroke, literature review for version 16.2

3. emedicine.com/neuro/topic9.htm

4. Up To Date : Antithrombotic treatment of acute ischemic stroke, literature review for version 16.2

5. A Guideline From the American Heart Association/ American Stroke Association 2007

Thank You!