Intensive care for

ischemic stroke

神經內科 洪國華

Content Treatment of acute ischemic stroke

Antithrombotics

IV rt-PA for ischemic stroke in MMH-TT

Guidelines in Taiwan Vs America

Specific treatment of various stroke syndrome

Large hemispheric infarction

Acute occlusion of basilar artery

Cerebellar infarction

腦中風的主要分類

缺血性中風的致病機轉

Source: G. W. Albers, etc Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh

ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (3 suppl.): 483S–512S

小動脈疾病

大動脈疾病

心因性

其他

怎麼辦ㄟ？

請告訴我抗血栓藥物分幾類？ Antiplatelets

Aspirin

Clopidrogel

Ticlopidine

Cilostazol

Anticoagulants

Heparin

LMW heparin

Coumadin

Dabigatran (Pradaxa)

Rivaroxaban (Xarelto)

Thrombolytics

斑塊破裂之發展史

Red clot

時間

可逆腦損傷

Benign Oligemia

救治缺血半陰影區是治療缺血性中風的首要目標

血流量 不可逆腦損傷

良性延遲供血區

把握黃金三小時

把握黃金60分鐘

腦中風急診病患處置流程三重點

啟動

急性腦中風

處置流程

急診護理師 □ 通知 Neuro

□ Vital signs

□ IV (N/S)抽血

□ EKG

神經內科醫師 □ NIHSS

□ 適用 iv tPA

□ 不適用 iv tPA

神經外科醫師 □ 手術

□ 不手術

急診醫師 □ Brain CT

□ 顱內出血？

□ iv tPA禁忌症？

檢傷護理師 □ FAST (

1.臨床懷疑是急性缺血性腦中風，中風時間明確在3小時內

2.腦部電腦斷層沒有顱內出血

3.年齡在18歲到80歲之間（年齡在18歲以下或80歲以上治療與否，應由醫師審慎評估病患整體狀況並與病患及家屬充份溝通後再作決定。）

急性中風靜脈注射rt-PA之收案條件

……罹患腦中風的病人只有不到三分之一的機會，可恢復到正常的功能。您若使用這種血栓溶解劑將會增加百分之三十三復原的機會…

…rt-PA是目前所能建議的最好治療方式，但有危險性：一百個使用這種血栓溶解劑rt-PA治療的病人，將會有六個病人(十倍於不用這種血栓溶解劑治療的病人)，可能引起腦部出血的危險，也可能會因而死亡。但是，研究顯示此種藥物，並不會增加死亡率……

急性中風靜脈注射rt-PA之病人告知書

Q:如何減少症狀性腦內出血的危險？

A:檢視過去病史、臨床現況、生化及影像所見

• 曾有顱內出血病史

• 過去對本藥之主成份Actilyse或賦型劑過敏者

• 最近3個月內有中風病史

• 最近3個月內有嚴重性頭部創傷

• 最近3個月內發生過急性心肌梗塞

• 最近21天內曾有胃腸道或泌尿系統出血

• 最近14天內曾動過大手術或有嚴重創傷

• 過去10天內曾對無法壓制之部位施行血管穿刺

（如鎖骨下或頸靜脈穿刺）

排除條件 1：過去病史（必須均為“否”）

Diagnosis of ischemic stroke causing measurable

neurological deficit

Onset of symptoms

Significant head trauma or prior stroke in previous 3 months

Symptoms suggest subarachnoid hemorrhage

Arterial puncture at noncompressible site in previous 7 days

History of previous intracranial hemorrhage

Intracranial neoplasm, arteriovenous malformation, or aneurysm

Recent intracranial or intraspinal surgery

Elevated blood pressure (systolic >185 mm Hg or diastolic >110 mm Hg)

Active internal bleeding

Acute bleeding diathesis, including but not limited to platelet 1.7 or PT >15 seconds

Current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated sensitive laboratory tests (such as aPTT, INR, platelet count, and ECT; TT; or appropriate factor Xa activity assays)

Blood glucose concentration 1/3 cerebral hemisphere)

Exclusion criteria for Patients With Ischemic Stroke Who Could Be

Treated With IV rtPA Within 3 Hours From Symptom Onset

Inclusion criteria

Diagnosis of ischemic stroke causing measurable neurological deficit

Onset of symptoms within 3 to 4.5 hours before beginning treatment

Relative exclusion criteria

Aged >80 years

Severe stroke (NIHSS>25)

Taking an oral anticoagulant regardless of INR

History of both diabetes and prior ischemic stroke

Acute Ischemic Stroke Who Could Be Treated

With IV rtPA Within 3 to 4.5 Hours

From Symptom Onset

() Class I; Level of Evidence B

(+) Class IIb; Level of Evidence C

CLASS I

好處 >>>壞處

CLASS IIa

好處 >>壞處

CLASS IIb

好處 ≥壞處

CLASS III

好處 <壞處

證據強度

Inclusion criteria

Diagnosis of ischemic stroke causing measurable neurological deficit

Onset of symptoms within 3 to 4.5 hours before beginning treatment

Relative exclusion criteria

Aged >80 years

Severe stroke (NIHSS>25)

Taking an oral anticoagulant regardless of INR

History of both diabetes and prior ischemic stroke

Acute Ischemic Stroke Who Could Be Treated

With IV rtPA Within 3 to 4.5 Hours

From Symptom Onset

() Class I; Level of Evidence B

(+) Class IIb; Level of Evidence C

Only minor or rapidly improving stroke symptoms (clearing

spontaneously)

Pregnancy

Seizure at onset with postictal residual neurological impairments

Major surgery or serious trauma within previous 14 days

Recent gastrointestinal or urinary tract hemorrhage (within

previous 21 days)

Recent myocardial infarction (within previous 3 months)

Relative exclusion criteriapatients may receive fibrinolytic therapy despite 1 or more

relative contraindications (Class IIb)

“Caution” instead of “contraindication”

• 曾有顱內出血病史

• 過去對本藥之主成份Actilyse或賦型劑過敏者

• 最近3個月內有中風病史

• 最近3個月內有嚴重性頭部創傷

• 最近3個月內發生過急性心肌梗塞

• 最近21天內曾有胃腸道或泌尿系統出血

• 最近14天內曾動過大手術或有嚴重創傷

• 過去10天內曾對無法壓制之部位施行血管穿刺

（如鎖骨下或頸靜脈穿刺）

排除條件 1：過去病史（必須均為“否”）

“Caution” instead of “contraindication”

“Caution” instead of “contraindication”

“Caution” instead of “contraindication”

• 發作的時間已超過3小時或症狀發作時間不明

• 症狀已迅速改善或症狀輕微（例如NIHSS＜4分）

• 嚴重之中風（例如NIHSS＞25）

• 中風發作時併發癲癇（影像檢查能確定為缺血性中風則不在此限）

• 收縮壓＞185 mmHg

• 舒張壓＞110 mmHg

排除條件2a：臨床現況（必須均為“否”）

“Caution” instead of “contraindication”

“Caution” instead of “contraindication”

“Caution” if 3 hours < onset < 4.5 hours

NIH Stroke Scale

西元1983年，由美國國家衛生研究院所發展

評估腦中風病患神經功能缺損的程度

評分結果：

0 No stroke symptom

1~4 Minor stroke

5~15 Moderate stroke

6~20 Moderate-to-severe stroke

21~42 Severe stroke

1. 清醒程度 0~3是否可以回答問題 0~2是否可以執行命令做動作 0~2

2. 眼球運動 0~23. 視野 0~34. 顔面麻痹 0~35. 左上肢運動 0~4

右上肢運動 0~46. 左下肢運動 0~4

右下肢運動 0~47. 肢體動作協調 0~28. 感覺障礙（痛覺、觸覺或空間感覺） 0~29. 言語障礙 0~310. 構音障礙 0~211. 感覺忽略 0~2

NIH Stroke Scale

• 顱內腫瘤、動靜脈畸形或血管瘤

• 出血性視網膜病變，如糖尿病性（視覺障礙可能為出血性視網膜病變的指標）或其他出血性眼疾

• 細菌性心內膜炎，心包炎

• 有懷疑主動脈剝離之證據

排除條件2b：臨床現況（必須均為“否”）

• 嚴重肝病，包括肝衰竭、肝硬化、肝門脈高壓（食道靜脈曲張）及急性肝炎

• 急性胰臟炎

• 身體任何部位有活動性內出血

• 其他（例如在排除條件未提到但會增加出血危險的狀況，如活動性肺結核、洗腎患者、嚴重心衰竭、身體太衰弱者或其他）

排除條件2c：臨床現況（必須均為“否”）

• 發作前48小時內使用heparin且aPTT過高

• 病人正接受口服抗凝血劑且INR＞1.7

• 血小板＜100,000 / mm3

• 血糖＜50mg/dl或＞400mg/dl（血糖>200mg/dl即須非常小心）

排除條件 3：生化所見（必須均為“否”）

• 影像評估為嚴重之中風（電腦斷層大於1/3中大腦動脈灌流區之低密度變化，或中線偏移）

排除條件 4：影像所見（必須均為“否”）

• 過去10天內分娩

• 控制不良之糖尿病

排除條件 5：其他（因風險增加，施打與否需與病患與家屬做充分溝通）

6

5

4

3

2

1

mRS=0

13%

7%

20%

20%

13%

27%

40%

47%

Favorable outcome

台東馬偕醫院急性腦梗塞病人靜脈溶栓治療之成果from July 2006 to June 2011

At 3 month follow-up

Modified Rankin Scale

Emergency Evaluation & Diagnosis of

Acute Ischemic Stroke

台東馬偕醫院急性腦梗塞病人靜脈溶栓治療之成果

缺血性中風經血栓溶解劑治療前24 小時的照顧原則(i)

盡快安排病人住進加護病房或同等級之病房

在用藥後24 小時內不要給抗凝血劑或抗血小板劑。若24 小時後有需要併用這些藥物時，需先做電腦斷層檢查，確定未有腦出血後再施予併用藥物。

除藥物外，禁食24 小時，24 小時內避免插鼻胃管。

24 小時內絕對臥床。

以N/S 500 cc keep IV route ，給2 l/min O2（需要時）, EKG monitor，紀錄I/O。

給藥後30 分鐘內儘量避免插尿管導尿，6 小時無解小便且膀胱腫漲厲害時，則需考慮單導或留置尿管。

Aspirin (initial dose is 325 mg) within 24 to 48 hours after stroke

(Class I; Level of Evidence A).

The usefulness of clopidogrel is not well established (Class IIb;

Level of Evidence C). Further research testing is required.

The efficacy of intravenous tirofiban and eptifibatide is not well

established (Class IIb; Level of Evidence C).

The administration of other intravenous antiplatelet agents that

inhibit the glycoprotein IIb/IIIa receptor (Abciximab) is not

recommended (Class III; Level of Evidence B).

Antiplatelet Agents 抗血小板藥物

Urgent anticoagulation, with the goal of preventing early

recurrent stroke, halting neurological worsening, or

improving outcomes after acute ischemic stroke, is not

recommended for treatment of patients with acute

ischemic stroke.

Urgent anticoagulation for the management of

noncerebrovascular conditions is not recommended for

patients with moderate-to-severe strokes because of an

increased risk of serious intracranial hemorrhagic

complications.

Anticoagulants 抗凝血劑(Class III; Level of Evidence A)

The usefulness of argatroban or other thrombin inhibitors

for treatment of patients with acute ischemic stroke is

not well established (Class IIb; Level of Evidence B). These

agents should be used in the setting of clinical trials.

The usefulness of urgent anticoagulation in patients with

severe stenosis of an internal carotid artery ipsilateral to

an ischemic stroke is not well established (Class IIb; Level

of Evidence B).

Anticoagulants 抗凝血劑New recommendations

缺血性中風經血栓溶解劑治療前24 小時的照顧原則(i)

盡快安排病人住進加護病房或同等級之病房

在用藥後24 小時內不要給抗凝血劑或抗血小板劑。若24 小時後有需要併用這些藥物時，需先做電腦斷層檢查，確定未有腦出血後再施予併用藥物。

除藥物外，禁食24 小時，24 小時內避免插鼻胃管。

24 小時內絕對臥床。

以N/S 500 cc keep IV route ，給2 l/min O2（需要時）, EKG monitor，紀錄I/O。

給藥後30 分鐘內儘量避免插尿管導尿，6 小時無解小便且膀胱腫漲厲害時，則需考慮單導或留置尿管。

缺血性中風經血栓溶解劑治療前24 小時的照顧原則(ii)

測量生命跡象（血壓、心跳、呼吸），每15 分鐘紀錄一次，持續2 小時，爾後每30 分鐘一次，持續6 小時，以後每60 分鐘一次，持續16 小時。

用藥完後2 小時及24 小時追蹤神經學檢查（包括NIHSS）。

注意有無出血傾向，尤其檢查穿刺處有無出血或血腫、在淤青處做範圍記號、檢查尿液有無出血。若血壓高於180/105mmHg 以上時，即需做處理，控制高血壓期間，需每15 分鐘監測一次血壓至血壓穩定。

若發現神經學功能惡化（NIHSS 增加4 分以上），懷疑有腦出血時，需立即做電腦斷層檢查，同時檢測CBC、PT（INR）、APTT，並準備4 單位的packed RBC或6 單位的cryoprecipitate、 2單位的FFP、1 單位的platelet。

Hemorrhagic Transformation of Cerebral Infarction

Hemorrhagic infarction (HI)

HI1 (small petechiae)

HI2 (confluent petechiae)

Parenchymal Hemorrhage (PH)

PH1 (≦ 30% of infarct)PH2 (> 30% of infarct)

General Principles of Neurologic Critical Care Clinical Examinations

Temperature management

Pulmonary Function and Mechanical Ventilation

Sedation and Analgesia

Fluid and Electrolyte Balance

Nutrition

Blood pressure control

Management of blood glucose

Be aware of deep vein thrombosis and pulmonary embolism

Treatment of IICP

Invasive monitor procedures

Specific Treatment of Various Stroke

Syndrome

Acute large hemispheric infarction

Acute basilar artery occlusion

Massive cerebellar infarction

Acute Large

MCA Stroke

Acute Large Middle Cerebral Artery

Stroke

Cardiac monitoring should be performed for at least the

first 24 hours (Class I; Level of Evidence B).

Supplemental oxygen should be provided to maintain

oxygen saturation >94% (Class I; Level of Evidence C).

Blood pressure management

In patients with BP > 220/120, a reasonable goal is to lower blood

pressure by 15% during the first 24 hours after onset of stroke.

(Class I; Level of Evidence C).

Autoregulation

Acute Large Middle Cerebral Artery

Stroke

IICP is a reliable prognostic sign

≈ 20 mmHg at the onset of deterioration

subsequently rise over next 24~48 hours

IICP > 30 mmHg is usually fatal

Moderate hypothermia reduce brain edemaa

Reduction of brain edema and control of ICP

Decompressive hemicraniostomy and duraplasty

Cerebral compliance

1. Decompressive surgical evacuation of a space-occupying

cerebellar infarction (Level of Evidence B)

2. Placement of a ventricular drain is useful in patients

with acute hydrocephalus secondary to ischemic stroke

(Level of Evidence C)

3. Decompressive surgery for malignant edema of the

cerebral hemisphere is effective and potentially

lifesaving (Level of Evidence B). Advanced patient age

and patient/family valuations of achievable outcome

states may affect decisions regarding surgery.

Class I recommendations for

surgical treatments

Hemicraniectomy & Duraplasty For Large

Hemispheric Infarction Or Malignant MCA Infarction

Should be held within 48 hours

after onset of stroke

5 Randomized Trials of Hemicraniectomy

& Duraplasty for Malignant MCA Infarction

HeADDFIRST (US)

HeMMI (Philippines)

HAMLET (Netherlands)

DECIMAL (France)

DESTINY (Germany)

Hemicraniectomy & Duraplasty for Malignant MCA Infarction

Inclusion criteria

• Age 18–60 years

• MCA infarction, including at least 2/3 of the territory and including at least part of the basal ganglia, with or without additionalipsilateral infarction of the ACA or PCA

• NIHSS score > 18 for lesions of the nondominant and > 20 for lesions of the dominant hemisphere

• Consciousness: drowsy or obtunded

• Onset of symptoms < 36 hours

• Start treatment/surgery within 6 hours

• Prestroke mRS score ≧ 2

• Prestroke score on the Barthel Index < 95

• Score on the Glasgow Coma Scale < 6

• Both pupils fixed and dilated

• Any other coincidental brain lesion that might affect outcome

• Space-occupying hemorrhagic transformation of the infarct

• Life expectancy < 3 years

• Other serious illness that might affect outcome

Hemicraniectomy & Duraplasty for Malignant MCA Infarction

exclusion criteria

5 patients will escape death and at 1 year

Mild disability = 1

Moderate disability = 1

Moderate-to-severe disability = 3 (unable to walk

independently)

For Every 10 Hemicraniectomies for

MCA Infarction

Acute Basilar

Artery Occlusion

Acute Basilar Artery Occlusion

2006 meta-analysis

Without recanalization, likelihood of good outcome= 2%

IA vs Iv thrombolysis

Recanalization rate= 65% vs 53%

Survival rate= 76% vs 78%

Good outcome= 24% vs 22%

Time window for recanalization < 6 or 12 hours?

May try bridging thrombolysis in combination of IV platelet GP IIb/IIIa antagonist tirofiban

a 44-year-old right-handed male,

5.5 h post onset of slurred speech, drowsiness, and left

hemiparesis

R.G. Gonzalez, J.A. Hirsch, W.J.Koroshetz,M.H.Lev, P. Schaefer:

Acute Ischemic Stroke: Imaging and Intervention p49

A clot in distal

basilar artery

Detection of Large Vessel Thrombus

CT Angiography

1. IV thrombolysis

rtPA

2. IA thrombolysis

rtPA, pro-urokinase, urokinase

3. Mechanical thrombectomy

Merci retriever

Penumbra aspiration system

Solitaire FR revascularization device

Trevor pro retriever

Recanalization strategies for acute ischemic stroke

Intravenous Fibrinolysissuccess rates of IV alteplase in recanalization

Alexandrov, A. V. (2010b). Current and future recanalisation strategies for acute ischemic

stroke (Review). J. Intern. Med. 267, 209–219.

9

Basilar artery: 30% [7]

Terminal part of the ICA: 6%[9]

M1 part of the MCA: 30% [4]

M2 part of the MCA: 44% [3]

Tandem ICA and MCA occlusion: 27%[5+6]

Atherosclerotic Plaque

粥狀硬化斑塊

Hansson et al. Nature Reviews Immunology 6, 508-519 (July 2006) | doi:10.1038/nri1882

纖維帽（fibrous cap）

富含脂肪的核心（lipid core）

破裂的斑塊

Merci Retriever

Interventional Management of Stroke III (IMS III) trial

Phase III randomized multicenter open-label clinical trial

IV rt-PA initiated within 3 h of stroke onset

Stopped after 656 of the intended 900 patients were enrolled for

there was a very low likelihood of finding a 10% difference in

favorable clinical outcome at 90 days (modified Rankin Scale score

of 0~2) in combined treatment arm

Endovascular Interventions

EKOs micro-infusion catheterprovides concurrent low-intensity ultrasound energy

Penumbra Aspiration System

Solitaire FR Revascularization Device

Trevo® Pro Retriever

The usefulness of emergent intracranial angioplasty and/or stenting is not well established. These procedures should be used in the setting of clinical trials (Class IIb; Level of Evidence C).

The usefulness of emergent angioplasty and/or stenting of the extracranial carotid or vertebral arteries in unselected patients is not well established (Class IIb; Level of Evidence C). Use of these techniques may be considered in certain circumstances, such as in the treatment of acute ischemic stroke resulting from cervical atherosclerosis or dissection (Class IIb; Level of Evidence C).

Endovascular InterventionsRecommendation

小腦梗塞可能造成阻塞性水腦症

小腦梗塞可能致使腦幹受壓迫

Cerebellar infarction

Neurologic deterioration growing mass effect of infarcted

cerebellum

Deterioration can occur within minutes

maximally on the 3rd day

can be any time within the 1st 2 weeks

Brainstem compression? Occlusive hydrocephalus? Concurrent brainstem stroke?

Decompressive surgery of post. fossa +/- removal of infarcted tissue 優於ventriculostomy (may promote ascending herniation)

Monitoring tools: BAEP and SSEP (Osmotherapeutics or decompressive surgery)

Take-home message

Treatment of acute ischemic stroke

Antithrombotics

IV rt-PA for ischemic stroke in MMH-TT

Guidelines in Taiwan Vs America

Specific treatment of various stroke syndrome

Large hemispheric infarction

Acute occlusion of basilar artery

Cerebellar infarction

Bye-bye!