Stroke in the ICUDr. Mohammad Aljawadi PharmD, Msc, PhD

PHCL 478Clinical Pharmacy Department

College of Pharmacy King Saud University

APRIL 2015

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Introduction

One of the top ten diseases that leads to death worldwide1

Can be classified:Acute ischemic stroke (85%)Acute hemorrhagic stroke (15%)

Around 15%-20% ends up treated in the ICU

Transient ischemic attack: Abrupt decrease in cerebral blood flow that does not cause permanent infarction.

1. Lopez AD, Mathers CD, Ezzati M et al (2006) Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367:1747–1757. doi: 10.1016/s0140-6736(06)68770-9

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Definition Abrupt onset of persistent neurologic symptoms caused by inadequate blood flow to a

particular area of the brain or by hemorrhage into the brain, which compresses brain tissue and secondarily compromises perfusion

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PathophysiologyIschemia due to different reasons will lead to the

creation of two areas: Ischemic core

Penumbral region

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PathophysiologyThe ischemic core:

Blood flow is too low to maintain electric activity

Multiple events happening simultaneously including: Energy failure

Disruption of ion homeostasis

Glutamate release

Calcium channel dysfunction

Free radical release

Mitochondrial dysfunction

Membrane disruption

Activation of inflammatory cascades

Necrosis and apoptosis

Associated with irreversible damage of neurons

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Pathophysiology The Penumbral region:

Hypo-perfused tissue

Capable of complete functional recovery if sufficient blood flow is restored quickly

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Matching GameWhich one is associated with what? Explain

DVT

Atrial Fibrillation

Stroke

Pulmonary Embolism

You can go in any direction

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Etiologies of acute ischemic stroke (AIS)Cardio-emobolic mainly due to atrial fibrillation (29%)

Atherosclerosis of cervical or intracranial vessels (16%)

Lacunar disease (16%)

Other: migraine, malignancy, and hypercoagulable states (3%)

Unknown (46%) mostly due to undiagnosed paroxysmal atrial fibrillation

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Lacunar strokeDue to occlusion of the fine arteries

that supply deep structures of the brain such as thalamus, basal ganglia or pons.

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NIH Stroke Scale (FYI) http://www.ninds.nih.gov/doctors/nih_stroke_scale.pdf

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The Oxford Stroke classification system (FYI)

The classification predicts the extent of the stroke, region affected, underlying etiology, and prognosis.

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Signs and symptoms (from the patient or his relative)

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Other S&S:

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Inside the ICU: ICH=intracerebral hemorrhage

SAH= Subarachnoid hemorrhage

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Therapy and Treatment recommendations:

1. Aspirin

2. Reperfusion Therapy

3. Stroke Unit

4. Decompressive craniectomy

Supporting Evidence of their benefit

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1) Aspirin

Aspirin 325 mg within 24-48 hours of stroke onset is associated with prevention of recurrent events

Clopidogrel or dipyridamole: these data do not provide solid evidence about the utility of these antiplatelet agents in the management of patients with acute ischemic stroke.

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2) Reperfusion Therapy

Reperfusion Therapy

Intravenous thrombolysis

Endovascular therapy

Purpose: To restore impaired blood flow to the ischemic penumbra before irreversible neuronal death occurs.

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2) Reperfusion Therapy:

Thrombolytics:Intravenous Tissue plasminogen activator (rt-PA):

Alteplase:▪ Should be given within the 4.5 hours of stroke onset

▪ First, rule out hemorrhagic stroke before administration

▪ 3-month favorable outcomes were:

▪ 2·55 (95% CI 1·44–4·52) for 0–90 min

▪ 1·64 (1·12–2·40) for 91–180 min

▪ 1·34 (1·06–1·68) for 181–270 min

▪ 1·22 (0·92–1·61) for 271–360 min in favor of the alteplase group.

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2) Reperfusion Therapy

Alteplase dosing:0.9 mg/kg (maximum total dose: 90 mg)

Patients ≤100 kg: Load with 0.09 mg/kg (10% of 0.9 mg/kg dose) as an IV bolus over 1 minute, followed by 0.81 mg/kg (90% of 0.9 mg/kg dose) as a continuous infusion over 60 minutes.

Patients >100 kg: Load with 9 mg (10% of 90 mg) as an IV bolus over 1 minute, followed by 81 mg (90% of 90 mg) as a continuous infusion over 60 minutes.

Initiation of anticoagulants (eg, heparin) or antiplatelet agents (eg, aspirin) within 24 hours after starting alteplase is not recommended

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2) Reperfusion TherapyAlteplase contraindications:

Risk factors for systemic bleeding: Systemic anticoagulation, recent major surgery, recent gastrointestinal or urinary tract hemorrhage,

prior arterial puncture at a non-compressible site within 7 days or evidence of a coagulopathy

Evidence of intracerebral or subarachnoid hemorrhage

BP is elevated (systolic blood pressure [SBP] > 185 mm Hg or diastolic blood pressure [DBP] > 110 mm Hg), as elevated blood pressure can increase the risk of hemorrhagic transformation

Serum glucose is < 50 or > 400 mg/dL as these conditions can cause focal neurologic signs that mimic stroke

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2) Reperfusion Therapy:Endovascular therapy:

Includes intra-arterial thrombolysis, mechanical embolectomy, and angioplasty/stenting Alternatives for IV rt-PA or patients who fail to improve after rt-PA

Intra-arterial thrombolysis within 6 hours of symptoms onset

Thrombectomy within 8 hours of symptoms onset

No difference between endovascular therapy (alone or with IV rt-PA) and IV rt-PA alone

Following reperfusion: Cranial imaging within 24 hours of reperfusion to detect hemorrhagic transformation

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Hemorrhagic transformation

Bleeding due to rt-PA useStop rt-PAuse of cryoprecipitate (source of fibrinogen), fresh frozen

plasma, and recombinant factor VII is not supported by robust evidence in this setting.

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2) Acute Stroke Unit:

Benefit of acute stroke unit1:Improved quality of careFacilitated patient access to thrombolysis and specialized stroke careTimely evaluationImproved early survival across age groupsMore cost-effective than care on other hospital wards/teamsReduced incidence of post-stroke complications, such as urinary tract

infections, pneumonia, and death.

1: http://www.strokeforum.com/acute-stroke-treatment/stroke-units.html

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2) Acute Stroke Unit:Characteristics of stroke unit:

Care provision by a multidisciplinary team with competencies in the management of stroke and its systemic complications

Coordinated multidisciplinary rehabilitation

Meetings between multidisciplinary team members

Regular educational and training programs

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2) Acute Stroke Unit:

Team:Neurologists

Nurses

Pharmacists

Neuro-surgeons

Physiotherapists

Occupational therapists

Speech therapists

Social workers

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MCA=middle cerebral artery

HOB=Head of the bed

In the ICU:

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Intensive care management of acute ischemic stroke

▪ Purpose: ▪ Monitoring and optimization

of systemic physiological homeostasis

▪ Monitoring and management of intracranial complications

▪ Includes:▪ Oxygenation

▪ Hemodynamic and fluid management

▪ Myocardial complications

▪ Glycemic control

▪ Fever

▪ Anticoagulation, antiplatelet therapy and thromboprophylaxis

▪ Neuromonitoring

▪ Cerebral edema and hemorrhage

▪ Seizures

▪ End-of-life care

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Indications for admission after AIS

Universal criteria are:• Decreased conscious level • Need for mechanical ventilation• Intensive hemodynamic management• Invasive neurological and systemic monitoring

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Oxygenation Continuous monitoring of oxygenation with pulse oximetry for all AIS patients on the

ICU.

Oxygen supplementation should be reserved for those with SpO2 <94 %.

Continuous monitoring of mechanical ventilation with regular arterial blood gas analysis.

Maintain normocapnea—target PaCO2 35–45 mmHg

All patients should undergo a formal swallow assessment

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Hemodynamics and fluid managementRegular noninvasive BP monitoring in all AIS patients on the ICU

There are no data to guide a specific BP target during the ICU management of AIS

BP lowering is not indicated in those not undergoing thrombolysis except:

220/120 mmHg

In the presence severe cardiac failure, aortic dissection or hypertensive encephalopathy

BP lowering should be cautious, i.e.,15 % in the first 24 h in those not receiving thrombolysis.

BP should be lowered 185/110 mmHg before and for at least 24 h after thrombolysis.

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Hemodynamics and fluid management Intravenous labetalol and nicardipine are reasonable first-line agents to lower BP.

Labetalol 10 to 20 mg over 1 to 2 minutes

Nicardipine :titrate by 2.5 mg/hour at 5- to 15-minute intervals (maximum dose: 15 mg/hour).

Sublingual nifedipine should be avoided as it can abruptly and inconsistently decrease BP.

If hypotension occurs: Fluid resuscitation

NE if unresponsive to IV fluids

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Myocardial complications post-AIS:

Include:Dysrhythmias are present in 57% of patients

Elevated cardiac troponins in 17.5%

Left ventricular dysfunction in 12%

Monitoring: ECG, cardiac tropnins

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Hyperglycemia:Hyperglycemia occurs in more than 40 % of AIS patients

Independently associated with increased mortality and morbidity at 90 days

Key recommendations: Regular blood glucose monitoring is essential.

Although tight glycemic control (72–135 mg/dl) has not been shown to result in deleterious outcomes, there is no evidence of clinical benefit in this population.

Treatment with continuous insulin infusion to maintain serum glucose between 140 and 180 mg/dl (8.0–10.0 mmol/l) is preferred on the ICU.

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FeverOccurs in almost 50% of patients after AIS

Independently associated with poor outcome

Key recommendations: Avoid pyrexia (T[37.5] Co).

Investigate for, and treat, infectious causes of fever.

Regular paracetamol (acetaminophen) therapy as a first line therapy in those with temperatures > 37.5 Co, the dose administered being dependent on local guidance.

Second-line therapy: IV metamizole, rapid infusion of cold saline (4 Co), and the use of automatic cooling systems.

Ibuprofen does not appear to reliably reduce body temperature after stroke

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Anticoagulation, antiplatelet therapy and thromboprophylaxis

Use of any anticoagulant is contraindicated in the first 24 h following thrombolysis, but should be considered after this.

Avoid AC in patients with moderate to severe stroke to avoid the development of hemorrhagic stroke

Prophylactic-dose subcutaneous LMWH to prevent DVT and mechanical intermittent calf compression.

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Cerebral edema and hemorrhage

One of the main intracranial complications post-AIS

Early detection is required since decompressive craniectomy, sometimes used to alleviate intracranial hypertension associated with malignant cerebral edema, is best performed early.

High Intracranial Pressure: Mannitol and hypertonic saline

There is no robust evidence that these improve outcome after AIS

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Others Seizure

Phenytoin has the most evidence

Levetiracetam started to be used in some centers

End of life decision Decision to resuscitate

Advanced directive

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Neuro-protectants Promising pre-clinical results

Disappointing clinical results due to: Heterogeneity of human stroke

Lack of consistency in methodological design

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Hemorrhagic Stroke:

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Questions

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http://en.wikipedia.org/wiki/Terri_Schiavo_case

http://www.ted.com/talks/jill_bolte_taylor_s_powerful_stroke_of_insight?language=en