Manage ischemic stroke pts

4,857 views

Published on

management of ischemic stroke pts

Published in: Health & Medicine
0 Comments
10 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
4,857
On SlideShare
0
From Embeds
0
Number of Embeds
7
Actions
Shares
0
Downloads
276
Comments
0
Likes
10
Embeds 0
No embeds

No notes for slide
  • General 6) Sodium nitroprusside 另一也同樣屬於 Nitrates 類的藥物, Sodium Nitroprusside ,它的作用機轉和 Nitroglycerin 相似,作用的 onset 及 Duration 都很理想,不過,降壓效果不易控制,需要多次的劑量調整,才能穩定的達到理想血壓,且 Sodium Nitroprusside 會產生有毒的代謝物,除此之外,因其具有光敏感性,所以在使用處理上須避光,並不方便。另外, Sodium Nitroprusside 雖然可以增加冠狀動脈血流,但卻有 Coronary artery steal 的現象,而無法救濟真正缺血的心臟組織。
  • General 7) Labetalol 這是一個同時具有  及  adrenergic recerptor 的阻斷劑( 7:1 ),因為在降壓的同時並不太會影響到 HR 和 CO ,且血壓控制很穩定,因此不需要進行 Monitor ,在 ICU 中經常使用。可是,其 Onset 太慢, Duration 太長,並不符合理想治療術中高血壓的條件,另外,因其阻斷  及  adrenergic recerptor 故會造成起立性低血壓及尿液滯留,也因為它是  Blocker ,所以也具有一切屬於  Blocker 之禁忌。
  • General 7) Labetalol 這是一個同時具有  及  adrenergic recerptor 的阻斷劑( 7:1 ),因為在降壓的同時並不太會影響到 HR 和 CO ,且血壓控制很穩定,因此不需要進行 Monitor ,在 ICU 中經常使用。可是,其 Onset 太慢, Duration 太長,並不符合理想治療術中高血壓的條件,另外,因其阻斷  及  adrenergic recerptor 故會造成起立性低血壓及尿液滯留,也因為它是  Blocker ,所以也具有一切屬於  Blocker 之禁忌。
  • Manage ischemic stroke pts

    1. 1. 1 Management of Acute Ischemic Stroke Patients Jiann-Shing Jeng, MD, PhD Stroke Center & Department of Neurology National Taiwan University Hospital, Taipei, Taiwan
    2. 2. Stroke Types: NTUH, 1995~20072 Large artery atherosclerosis 12% Small artery lacune Subarachnoid 22% hemorrhage 6% Cardioembolism 14% Cerebral hemorrhage Other determined 22% Undetermined 4% 20%
    3. 3. Stroke Chain of Survival3  Detection Recognition of stroke signs/symptoms  Dispatch Call 119 and priority EMS dispatch  Delivery Prompt transport and prehospital notification to hospital  Door Immediate ED triage  Data ED evaluation, prompt laboratory studies, and CT imaging  Decision Diagnosis and decision about appropriate therapy  Drug Administration of appropriate drugs or other intervention
    4. 4. EMS in Acute Stroke4  Rapid identification of acute stroke  Elimination of comorbid conditions mimicking stroke  Stabilization  Rapid transportation  Notification of receiving institution
    5. 5. Prehospital Stroke Identification5  Los Angeles Prehospital Stroke Screening  Cincinnati Prehospital Stroke Scale
    6. 6. Los Angeles Prehospital Stroke Screen (LAPSS)6  Last time patient known to be symptom free  Screening criteria 1. Age >45 y 2. No history of seizure or epilepsy 3. Symptom duration less than 12 hours 4. No previously bedridden or wheelchair bound 5. Blood glucose 60-400 mg/Dl 6. Exam:  Facial smile/grimace: normal, droop  Grip: normal, weak grip, no grip  Arm strength: normal, drifts down, falls rapidly
    7. 7. LOS ANGELES MOTOR SCALE (LAMS)7 Normal Right Left Total Facial Ͱ Droop (1) Ͱ Droop (1) Ͱ (0) smile/grimace Ͱ Weak grip (1) Ͱ Weak grip (1) Grip Ͱ (0) Ͱ No grip (2) Ͱ No grip (2) Ͱ (0) Ͱ Drifts down (1) Ͱ Drifts down (1) Arm strength Ͱ Falls rapidly (2) Ͱ Falls rapidly (2) TOTAL Score
    8. 8. Cincinnati Prehospital Stroke Scale8  Facial droop  Normal : both sides of face more equally  Abnormal : one side of face does not move as well as the other  Arm drift  Normal : both arms move the same or both arms do not move at all  Abnormal : one arm either does not move or drift down compared to the other  Speech  Normal : says correct words with no slurring  Abnormal : slurs words, says the wrong words, or is unable to speak
    9. 9. How to approach a patient with probable acute stroke?9  New onset of acute  Subsequent hospital neurological deficit management  Differential diagnosis of other  Acute stroke non-stroke diseases management  Establish cause of  Initial ER assessment and stroke management  Stroke risk factors  Vital signs, sugar  Dysphagia screening  Consciousness: GCS  Early rehabilitation  Non-contrast head CT  PT, OT, ST  Stroke severity: NIHSS  Plan for secondary  Stroke type and location prevention of stroke  Hyperacute management Thrombolytic therapy Craniectomy Intensive care/monitoring
    10. 10. History for initial diagnosis of acute stroke10  Rapid, accurate history taking  Often from the family members  Key elements of history  Onset time: the last time of normal neurological status  Onset mode: sudden, acute, subacute  Onset symptoms: focal or generalized symptoms  Course: progression of symptoms  Co-morbid diseases: HTN, DM, Heart diseases, etc.  Use of medications: antiplatelets, anticoagulants, antihypertensives, insulin, etc.
    11. 11. Misdiagnosis of Acute Stroke ~ NTUH experience11 No. % Acute stroke 2226 87.6 Misdiagnosis of acute stroke 316 12.4 Possible neurovascular disorders 57 2.2 Other neurological disorders 209 8.2 Non-neurological disorders 50 2.0 Total 2542 100.0
    12. 12. Differential Diagnosis of Acute Stroke12  Old cerebrovascular disease  Craniocerebral/cervical trauma  Meningitis/encephalitis  Hypertensive encephalopathy  Intracranial mass (tumor, subdural/epidural hematoma)  Seizure with persistent neurological signs (Todd’s paralysis)  Vestibulopathy  Spinal cord or peripheral nerve lesions  Migraine with persistent neurological signs  Metabolic:  Hyperglycemia  Hypoglycemia  post-cardiac arrest hypoxia  Infection  Drug overdose, etc.
    13. 13. NTUH ER Stroke Assessment: History13 Stroke/TIA Onset Time: 確定 年 月 日 時 分 不確定 Stroke/TIA Onset Symptoms: drowsiness, stupor, delirium, coma, headache, vomiting, neck stiffness, seizures, anopia, aphasia ( sensory, motor), apraxia, vertigo, dizziness, dysarthria, dysphagia, diplopia, ataxia, incontinence left side weakness ( face, upper limb, lower limb), right side weakness ( face, upper limb, lower limb), left side numbness ( face, upper limb, lower limb), right side numbness ( face, upper limb, lower limb), Others: Stroke/TIA Onset Mode: sudden, acute, fluctuating course Activity at Stroke/TIA Onset: strenuous activity, ordinary activity, rest, sleep Stroke in Progression: yes (symptoms progression>1 hour), no
    14. 14. NTUH ER Stroke Assessment: NIHSS14 1a. Level of Consciousness (LOC) 4. Facial Palsy 7. Limb Ataxia □ 0= Alert □ 0= Normal □ 0= Absent □ 1= Not alert, but arousable □ 1= Minor □ 1= Present in one limb. □ 2= Not alert, obtunded □ 2= Partial □ 2= Present in two limbs □ 3= Uunresponsive □ 3= Complete 8. Sensory 1b. LOC Questions 5a Left Motor Arm □ 0= Normal □ 0= Answers both questions □ 0= No drift □ 1= Mild to moderate sensory loss correctly □ 1= Drift □ 2= Severe □ 2= Some effort against gravity □ 1= Answers one question correctly 9. Best Language □ 3= No effort against gravity □ 2= Answers neither question □ 4= No movement □ 0= normal correctly 5b. Right Motor Arm □ 1= Mild to moderate aphasia 1c. LOC Commands □ 0= No drift □ 2= Severe aphasia □ 0= Performs both tasks correctly □ 1= Drift □ 3= Mute, global aphasia □ 1= Performs one task correctly □ 2= Some effort against gravity 10. Dysarthria □ 2= Performs neither task correctly □ 3= No effort against gravity □ 0= Normal 2. Best Gaze □ 4= No movement □ 1= Mild to moderate □ 0= Normal 6a. Left Motor Leg □ 2= Severe □ 1= Partial gaze palsy □ 0= No drift 11. Extinction and Inattention □ 2= Forced deviation or total gaze □ 1= Drift □ 0= Normal paresis □ 2= Some effort against gravity □ 1= One sensory modality 3. Visual □ 3= No effort against gravity □ 2= More than one sensory modality □ 0= No visual loss □ 4= No movement □ 1= Partial hemianopia. 6b. Right Motor Leg □ 2= Complete hemianopia □ 0= No drift Total Score: □ 3= Bilateral hemianopia □ 1= Drift □ 2= Some effort against gravity □ 3= No effort against gravity □ 4= No movement
    15. 15. NTUH ER Stroke Assessment: Diagnosis15 Head CT Findings: □Hemorrhage □Ischemia Early sign: Diagnosis: □Ischemic Stroke (□ left, □right ) □ACA; □MCA, total; □MCA, partial; □PCA; □Brainstem, □cerebellum □Hemorrhagic Stroke (site: ) □Others: Management Suggestion:
    16. 16. Head images for acute stroke diagnosis16 Everyone with suspected stroke  CT without contrast Some patients required stroke mechanism realization or treatment consideration  MRI  MRA  CTA  Ultrasound (duplex, transcranial Doppler, Echocardiography)  Conventional angiography
    17. 17. Early CT signs in acute MCA stroke17 Left and middle: Hyperdense left MCA sign (yellow arrow), hypoattenuated left basal ganglia (red arrow), and cortical swelling (blue arrows) in the same patient. Right: Dot sign (yellow arrow) in the left sylvian fissure.
    18. 18. Alberta Stroke Program Early CT Score (ASPECTS)  Quantify the extent of CT hypodensity in acute stroke A M1 C I L M2 IC M3 P Barber et al. Lancet. 2000;355:1670-4.
    19. 19. Diagnosis of Acute Stroke19  Stroke vs. non-stroke  Infarction or hemorrhage  Infarction  Location diagnosis  Arterial territory diagnosis  Pathophysiology diagnosis  Etiology diagnosis
    20. 20. Location Diagnosis of Stroke20  Supratentorial site  Hemisphere side  Cortical or subcortical areas  Frontal, parietal, temporal lobe  Infratentorial site  Midbrain, pons, medulla, cerebellum
    21. 21. Arterial Territory Diagnosis of Stroke21  ICA: more than MCA territory  ACA  MCA  Lenticulostriate artery  Cortical branches  Internal borderzone area  PCA  External borderzone area  V-B system  Extracranial VA  Intracranial  VA, BA, PICA, AICA, SCA
    22. 22. Acute Stroke Case22 A 70-year-old, right-handed man has been known to have previous history of poorly controlled hypertension, diabetes, and cardiac arrhythmia. He developed abrupt onset of left-sided weakness after dinner at 7 pm. What should you do?
    23. 23. Acute Stroke Case23 He brought to a medical center ER by the EMS at 8:30 pm. On initial ER arrival, his consciousness was awake, blood pressure was 210/120 mmHg, pulse rate was 120/min irregularly, respiratory rate was 20/min, body temperature was 37°C and blood sugar was 320 mg/dL. What should you do if you are on duty at ER ?
    24. 24. Acute Stroke Case24 Neurologically, he had flaccid hemiplegia and right- sided gaze preference with dense left-sided hemineglect. The NIHSS score was 17. Head CT scan revealed effacement of cortical sulcal marking in the right middle cerebral artery territory and hyperdense MCA sign. What is your diagnosis of the stroke ? What are the next you will do ?
    25. 25. Diagnosis of Acute Stroke25  Stroke  confirmed by history and images  Infarction  confirmed by head CT  Location  right MCA territory (>1/2)  Arterial territory  right MCA, main trunk  Pathophysiology  embolism  Etiology  cardioembolism, atrial
    26. 26. Arterial OcclusionEmbolism Site Microembolus Atheroma
    27. 27. Stroke Evaluation Targets for Potential Thrombolytic Candidates27 Time Target Door to doctor 10 minutes Door to CT completion 25 minutes Door to CT read 45 minutes Door to treatment 60 minutes Assess to neurological expertise 15 minutes Assess to neurosurgical expertise 2 hours Admit to monitored bed 3 hours
    28. 28. Acute Ischemic Stroke Protocol28 ER arrival Triage nurse confirm stroke onset time < 4 hours ER Resident performs Rapid evaluation (5 minutes) Neurology Resident receives 1.exact time of onset ER stroke page and 2.important history proceeds to ER 3.quick neurological evaluation brief history & physical exam STAT CT and blood work Page Stroke VS Head CT findings, laboratory data, NIH stroke scale Confirm the criteria fulfilling thrombolytic therapy for ischemic stroke Family’s agreement for thrombolytic therapy Stroke onset < 3 hours Stroke onset 3-6 hours Call Neuroradiologists IV-tPA treatment IA thrombolytic therapy IA thrombolysis Patient is admitted to Stroke ICU for intensive monitoring/care
    29. 29. Essentials of Acute Stroke Care29  Acute stroke team  Multi-disciplinary care  Stroke units  Intensive care of stroke patients  Standardized protocol of acute stroke management  Early rehabilitation of acute stroke patients
    30. 30. Acute Stroke Teams30  Acute stroke team consists of health care professional with experience and expertise in stroke  Available 24 hours everyday, within 15 minutes of the call  At a minimum, a qualified acute stroke physician and another health care professional
    31. 31. Stroke Units31  A setting designed for the care of stroke  Admission/discharge criteria, patient census and outcome data  Staffed and directed by personnel (physicians, nurses, etc.) with training and expertise in caring for patients with cerebrovascular disease  Equipment and written protocols for stroke patient care: Neuro, Cardiac, B/P monitoring
    32. 32. Potential Benefits of Stroke Units32 50 Cases saved from death and dependency 45 40 35 per 1,000 events 30 25 20 15 10 5 0 Stroke unit ASA tPA <3h tPA <6h Neuroprotective agents Gilligan et al. Cerebrovasc Dis. 2005;20:239-44.
    33. 33. Goal of Acute Ischemic Stroke Care33 Treatment goals Therapeutic strategies To reverse brain ischemia before it cause Recanalization, esp. permanent brain injury thrombolysis To prevent stroke in evolution and recurrence Antithrombotic agents To optimize the patient’s medical condition and Homeostasis of the brain prevent the common medical sequelae that occur after stroke or after a stroke intervention To optimize functional recovery after the Early rehabilitation residual permanent injury that has occurred
    34. 34. Homeostasis of the Brain34  Blood pressure  SBP 120-220 mmHg, DBP 70- 110 mmHg  Blood glucose level  blood sugar 100-150 mg/dL  Body temperature  <37.5°C  Oxygen saturation  >95%
    35. 35. Blood Pre s s ure in Ac ute Is c he mic S troke35  A spontaneous increase in BP is common in patients with acute ischemic stroke, and the increase in BP tends to be more pronounced in patients with preexisting hypertension.  Elevations in systolic blood pressure >160 mm Hg are detected in 60% of patients with acute stroke.
    36. 36. C aus e of Ele vate d Blood Pre s s ure in Ac ute S troke36  Stress of hospitalization  Stress of the cerebrovascular event  A full bladder, nausea, pain, other body discomfort  Preexisting hypertension  A physiological response to hypoxia  A response to increased intracranial pressure
    37. 37. Blood Pre s s ure in Ac ute Is c he mic S troke37  In a majority of patients, BP tends to decline in the first few days to weeks after stroke onset, even without pharmacological intervention.  A significant decline in BP can be seen in approximately a third of patients in the first few hours after stroke onset.
    38. 38. Blood Pre s s ure in Ac ute Is c he mic S troke38  BP often falls spontaneously when the patient is moved to a quiet room, the patient is allowed to rest, the bladder is emptied, or the pain is controlled.  In addition, treatment of increased intracranial pressure may result in a decline in BP.
    39. 39. Time course of blood pressure (MAP) with acute ischemic stroke39 Christensen et al. Acta Neurol Scand 2002;106:142-7.
    40. 40. Admission Blood Pressure and Outcome ~ International Stroke Trial40 Leonardi-Bee et al. Stroke 2002;33:1315-20.
    41. 41. High Blood Pressure in Acute Stroke and Outcome41  For every 10-mm Hg increase >180 mm Hg, the risk of neurological deterioration increased by 40% and the risk of poor outcome increased by 23%
    42. 42. Cerebral Perfusion Pressure42  Cerebral perfusion pressure (CPP) = Mean arterial blood pressure (MABP) – intracranial pressure (ICP)  Maintain CPP >60 mm Hg to ensure cerebral blood flow  In case of elevated ICP, elevated BP is required for maintaining adequate CPP.
    43. 43. Management of Elevated BP in Acute Ischemic Stroke43  Current recommendation based on the type of stroke  Antihypertensive therapy in acute ischemic stroke  Aggressive antihypertensive therapy may lower the cerebral perfusion pressure and lead to stroke worsening  Acute stroke patient may have exaggeration of response to antihypertensive agents  For nonthrombolytic candidates Not to treat if SBP <220, DBP <120, or MAP <130 mm Hg.  For thrombolyic candidates Not to treat if SBP <185, or DBP <110 mm Hg
    44. 44. BP Lowe ring in Ac ute Is c he mic s troke44  When treatment is indicated, lowering the BP should be done cautiously.  Some strokes may be secondary to hemodynamic factors, and a declining BP may lead to neurological worsening.
    45. 45. Blood Pressure Management of Ischemic Stroke (nonthrombolytic candidates)45 Blood pressure Treatment DBP >140 mm Hg Sodium nitroprusside (0.5 ug/kg/min). Aim for 10-20% reduction in DBP. SBP >220, DBP >120, or 10-20 mg labetalol IV push over 1-2 min. MAP >130 mm Hg May repeat or double labetalol every 20 min to a maximum dose of 150 mg. SBP <220, DBP <120, or Emergent antihypertensive therapy is MAP <130 mm Hg deferred in the absence of aortic dissection, acute myocardial infarction, severe congestive heart failure, or hypertensive encephalopathy
    46. 46. Intravenous Medications Considered for Control of Elevated BP in Patients With ICH ~ AHA, 200746 Drug Bolus Dose Continuous Infusion Rate Labetalol 5~20 mg every 15 min 2 mg/min (maximum 300 mg/d) Nicardipine NA 5~15 mg/h Esmolol 250 μg/kg IV push loading dose 25~300 μg/kg/min Enalapril 1.25~5 mg IV push every 6 h* NA Hydralazine 5~20 mg IV push every 30 min 1.5~5 μg/kg/min Nipride NA 0.1~10 μg/kg/min Nitroglycerin NA 20~400 μg/min Broderick et al. Stroke. 2007;38.
    47. 47. Common Intravenous Anti- Hypertensive Drugs Use in ICU47  Sodium Nitroprusside (Nipride)  Direct vasodilation  Labetalol (Trandate)  β and α-1 blockade  Nicardipine (Perdipine)  Calcium channel blockade
    48. 48. Sodium Nitroprusside48 Mechanism : Direct artery and vein dilation Administration : IV infusion Onset : Seconds Duration : Continuous, during infusion Advantage : Balanced ↓ of preload & afterload Disadvantage : 1. Excessive hypotension 2. Reflex tachycardia 3. Light sensitivity 4. Potential cyanide/thiocyanate toxicity Dosage : 0.25-10 µg/kg/min IV
    49. 49. Labetalol49 Mechanism : β and α-1 blockade Administration : Bolus/infusion Onset : bolus -- 5~30 min, infusion -- 15~60 min Duration : 2~12 hrs Advantage : 1. Little change in HR and CO 2. Intra-A or ICU monitoring (-) Disadvantage : 1. Orthostatic hypotension 2. Urinary retention 3. β-blocker’s contra-indications Dosage : 10-80 mg IV q10 min up to 300 mg, IV infusion: 0.5-2 mg/min
    50. 50. Nicardipine50 Mechanism : Calcium blockade, endothelin-1 antagonism Administration : Bolus/infusion Onset : 1-5 min Duration : 3~6 hrs Advantage : 1. no interference with CBF, CO 2. diuretic effect 3. inhibit platelet aggregation, vasospasm Disadvantage : 1. hypotension 2. bradycardia Dosage : 5 mg/h IV, 2.5 mg/h q15 min, up to 15 mg/h
    51. 51. Blood Glucose within the first 48 hours after stroke51  124 patients with ischemic stroke without previously diagnosed diabetes had blood glucose measured at least 4-hourly until 48 hours poststroke.  The mean glucose was 6.6 mmol/L throughout the period of monitoring, with no change over time.  More severe stroke and glucose-lowering therapy to be associated with higher poststroke glucose levels. Wong et al. Neurology 2008;70:1036-41.
    52. 52. Poststroke Hyperglycemia52  Persistent hyperglycemia  Definition: mean blood glucose >7 mmol/L (126 mg/dL) or HbA1C >6.2%  An independent determinant of infarct expansion  Associated with worse functional outcome Baird al. Stroke. 2003;34:2208-14.
    53. 53. Intensive Insulin Therapy in the Medical ICU53  A prospective, randomized, controlled study of 1,200 adult patients admitted to the medical ICU.  Comparison between conventional therapy (insulin administered when blood glucose >215 mg/dL) and intensive therapy (blood glucose control within 80-110 mg/dL)  Intensive insulin therapy significantly reduced morbidity among all patients in the medical ICU. Van den Berghe et al. N Engl J Med. 2006;354:449-61.
    54. 54. Respiratory Failure in Acute Stroke Patients54  Major causes  Prognosis: poor in  Aspiration pneumonia 49-93%  Impaired central respiratory drive  Respiratory function  Neurogenic pulmonary  Risk for aspiration, edema airway obstruction,  Overall stroke: 10% hypoventilation.  Ischemic stroke: 5-6%  Target at O2  ICH: 26-30% saturation > 95%  SAH: 47%
    55. 55. Fever and ischemic stroke55  Fever correlates with increased severity of stroke, mortality, and poorer prognosis in patients with ischemic stroke  Differentiation of the fever causes  central, drug, infection, etc.  Hyperthermia  May accelerate cerebral metabolism and neuronal injury  A marker of severity of stroke or a consequence of large strokes is unclear  Mild hypothermia  Improve neurological outcome  Reduce elevated ICP
    56. 56. Causes of Intracranial Hypertension56  Intracranial mass  Cerebral edema  Cytotoxic (intracellular)  Vasogenic (extracellular)  Cerebrospinal fluid hypervolemia  Decreased absorption  Overproduction of CSF  Increased intracranial blood volume  Cerebral vasodilatation (hypoxia, hypercapnia)  Obstructed venous outflow
    57. 57. IICP Management in Acute Ischemic Stroke57 General  Osmotherapy  cardiopulmonary and  Mannitol metabolic support  Glycerol  Positioning:elevate head of  Hypertonic saline the bed to 30o  Hyperventilation  Treat fever  Surgery  Treat seizure  Drainage of  Avoidhypoxia and cerebrospinal fluid: hypercapnia ventriculostomy, VP shunt  Avoid hypo-osmolar fluids  Craniectomy  Avoid hyperglycemia
    58. 58. Medical Therapy in Acute Ischemic Stroke58  Thrombolytic therapy  IV rt-PA therapy  IA rt-PA or urokinase therapy  Combined IV and IA thrombolysis  Antithrombotic therapy  Antiplatelets: aspirin, clopidogrel (Plavix), Aggrenox  Anticoagulants: heparin, low-molecular weight heparin, warfarin  Neuroprotection: uncertain effect
    59. 59. Territory infarct vs. borderzone infarct59
    60. 60. Penumbrae of Ischemic Stroke60  Penumbrae is the target of any reperfusion therapy  The fate of brain tissue depends on  Time  Cerebral blood flow  Occluded arterial flow  Collateral blood flow  Time is brain
    61. 61. Outcomes in rt-PA-treated Patients Compared with Controls at 3 M After Stroke61 NINDS rt-PA Study Group. NEJM 1995;333:
    62. 62. IV Thrombolysis of Acute Ischemic Stroke ~ Cochrane Meta-Analysis62 death or dependency (mRS 3-6) death or dependency (mRS 3-6) treated up to 3 h after stroke treated up to 6 h after stroke
    63. 63. Model Etimating OR for Favourable Outcome at 3 M in rt-PA-treated Patients Compared with Controls63 Hacke et al. Lancet 2004;363:768-774
    64. 64. Cochrane thrombolysis meta-analysis symptomatic (including fatal) intracranial hemorrhage64
    65. 65.  Outcome in SITS-MOST and Pooled Randomised Controlled Trials at 3 M After Stroke Onset65 Wahlgren et al. Lancet 2007;369:275-82.
    66. 66. ECASS III : IV rt-PA 3~4.5 hours Distribution of Scores on the Modified Rankin Scale66Hacke et al. N Engl J Med. 2008;359:1317-29.
    67. 67. ECASS III : IV rt-PA 3~4.5 hours Odds Ratios for Functional End Points at Days 90 and 30 after Treatment67 Hacke et al. N Engl J Med. 2008;359:1317-29.
    68. 68. IV tPA for Acute Ischemic Stroke ~ Inclusion Criteria68  Ischemic stroke with clearly defined symptom onset  Measurable deficit on the NIH Stroke Scale  Age >18 years  No evidence of intracranial blood on the brain CT scan  Timing from the symptom onset to initiate of IV rt-PA  NINDS (1995) : <3 hours  ECASS-III (2008) : <4.5 hours
    69. 69. IV tPA for Acute Ischemic Stroke ~Exclusion Criteria69  Rapidly improving or minor stroke symptoms (NIHSS <4)  Severe stroke symptoms by clinical (e.g., NIHSS >25) or head CT scan (> 1/3 MCA low density)  Stroke or serious head trauma within 3 mo  Major surgery within 14 d  History of intracranial hemorrhage  Systolic BP >185 mmHg or diastolic BP >110 mmHg of treatment initiation  Aggressive BP treatment (i.e., continuous IV infusion of antihypertensive to achieve above goal)
    70. 70. IV tPA for Acute Ischemic Stroke ~Exclusion Criteria70  Suspected SAH despite a normal CT scan  Gastrointestinal or urinary tract hemorrhage within 21 d  Arterial puncture at a noncompressive site within 7 d  Seizure at the onset of stroke with uncertain new stroke  Use of heparin within 48 h and an elevated PTT-aPTT  Old stroke with diabetes mellitus  Use of warfarin and INR >1.7  Platelet count < 100,000/mm3  Glucose < 50 or > 400 mg/dL
    71. 71. Guidelines for IV thrombolysis ~ Care during the first 24 hours after administration of tPA71  Admission to a skilled care facility (ICU or acute stroke unit)  Careful monitor and management of BP  Keep SBP<185 mmHg, DBP<110 mmHg  No use of anticoagulants and antiplatelet  Central venous access and arterial punctures are restricted  Placement of an indwelling bladder catheter should be avoided during drug infusion and for at least 30 minutes after infusion ends  Insertion of a nasogastric tube should be avoided  Careful neurological evaluation (NIHSS at 1st, 2nd, 24th hours)
    72. 72. Risk of hemorrhagic changes72  Marked hyperglycemia  Higher NIHSS score or DM  Longer time to  CT >1/3 MCA recanalization  Increasing stroke  Lower platelet counts severity  Higher glucose level at  Low platelet counts admission ~ Circulation. 2002 ~ Stroke. 2002
    73. 73. Guidelines for IV Thrombolysis ~ Bleeding Management73  Head CT should be obtained on an emergent basis whenever neurological worsening (NIHSS increase >4)  Any life-threatening hemorrhagic complication, including ICH, should be followed by these sequential steps:  Discontinue ongoing infusion of thrombolytic drug  Obtain blood samples for coagulation tests  HCT, HB, PT/INR, PTT, PLT, Blood type  Obtain surgical consultation, as necessary  Consider other interventions that may be useful, such as transfusion 4 units packed RBC, 2 units FFP, 6 units cryoprecipitate, 1 unit PLT
    74. 74. IV rt-PA in Acute Ischemic Stroke Case Presentation72 female, HT, CAD, AF, Sudden left hemiplegiaInitial NIHSS (1 hour): 19NIHSS 1 week later: 8Hemorrhagic transformation (asymptomatic) of right MCA territory
    75. 75. IV rt-PA in Acute Ischemic Stroke Case Presentation65 year-old female, no known major systemic diseasesAcute onset, left hemiplegia, neglect, and hemianopia.ER arrival in 1 hour. Initial NIHSS: 1524 hours after IV-tPA therapy: NIHSS: 3Discharge (10 days later): NIHSS: 0, mRS: 0, Barthel index: 100
    76. 76. Intra-arterial Thrombolysis76 M2 superior division Microcatheter Thrombus MCA, M1 ICA M2 inferior division
    77. 77. Intra-arterial Thrombolysis77
    78. 78. Intra-arterial Thrombolysis78  Advantage  Higher recanalization rate  Symptomatic brain hemorrhage  8.3% in the carotid system  6.5% in vertebrobasilar territory  No higher than those in IV thrombolysis  Disadvantage  Ready availability of neuro-interventionalists, a stroke team, and a stroke ICU  Additional time required to begin treatment compared to IV thrombolysis
    79. 79. Mechanical Clot Disruption and Removal – 121 patients with MCA infarct less than 6 h – Some also received IA thrombolysis – Median NIHSS was 19, 40% had baseline NIHSS >20 – 114 were treated with MERCI device – Recanalization rate: 54% – Symptomatic brain hemorrhage: 8% • 5% with retriever alone, 24% with retriever and IA thrombolysis – Mortality at 3 mo: 40% Stroke 2005;36:1432-8. After the microcatheter transverses the thrombus, the first loops of the Merci Retriever are delivered distal to the occlusion site. The Merci Retriever is pulled back at the contact of the thrombus, additional loops are delivered within the thrombus, and the Merci Retriever is torqued to ensnare the thrombus. The balloon of the balloon guide catheter (BGC) (insert) is inflated to control antegrade flow, and the Merci Retriever is pulled back with the ensnared thrombus toward the tip of the BGC where it is aspirated.
    80. 80. Ultrasound-Enhanced Thrombolysis80  Intra-venous rt-PA thrombolysis and continuous 2-MHz transcranial Doppler ultrasonography <3 hours after stroke onset  Augment arterial recanalization  Increased neurological recovery Alexandrov A et al. N Engl J Med 2004;351:2170-2178
    81. 81. Future Treatment of Acute Ischemic Stroke81  New thrombolytic agents  Combined IV+IA thrombolysis  IV tPA within 3 h, IA tPA 3-6 h  Combined thrombolytic agents and antiplatelets  Combined thrombolytic agents and anticoagulant  Neuroprotection agents  MRI diffusion-perfusion mismatch  3-9 h after stroke onset  Clot/thrombus retrieval
    82. 82. Ischemic Penumbra
    83. 83. Current available antithrombotic agents for acute ischemic stroke83  Oral antiplatelet agents  Heparins  Aspirin  Unfractionated heparin  Ticlopidine  Low-molecule-weight  Clopidogrel heparins  Dipyridamole  Dalteparin  Aspirin + extended-release  Enoxaparin dipyridamole  Cilostazol  Tinzaparin  Heparinoids  Glycoprotein IIb/IIIa  Danaparoid inhibitors  Abciximab  Direct thrombin  Tirofiban inhibitors  Epifibatide  Argatroban  Bivalirudin  Lepirudin
    84. 84. Antiplatelet in Acute Ischemic Stroke84  International Stroke Trial (IST)  19,436 patients, ASA 300 mg/day, <48 hors  Chinese Acute Stroke Trial (CAST)  21,106 patients, ASA 160 mg/day, <48 hours  Combined analysis of ASA vs placebo  Absolute risk reduction reduction of deaths or nonfatal stroke: 0.9%  Absolute risk reduction reduction of early stroke recurrence: 0.7%  Small increase in ICH or systemic hemorrhage: IST (1.1% vs 0.6%), CAST (0.8% vs 0.6%) Stroke 2002;33:1934-42
    85. 85. Effect of various therapies for treatment of acute ischemic strokeAgent Trial Outcome EffectAspirin IST Hemorrhagic stroke at 2 wk Harm of 1 per 1000 (NS) Death or nonfatal stroke at 2 wk Benefit of 11 per 1000 (p<0.05) Dead or dependent at 6 mo Benefit of 13 per 1000 (p=0.07) CAST Hemorrhagic stroke at 2 wk Harm of 2 per 1000 (NS) Death or nonfatal stroke at 1 mo Benefit of 7 per 1000 (p=0.03) Dead or dependent at 1 mo Benefit of 11 per 1000 (p=0.08)Heparin IST Recurrent ischemic stroke at 2 wk Benefit of 9 per 1000 (p<0.01)(any dose) Hemorrhagic stroke at 2 wk Harm of 8 per 1000 (p<0.0001) Major extracranial hemorrhage Harm of 9 per 1000 (p<0.0001) Pulmonary embolism Benefit of 3 per 1000 (p<0.05) Death or nonfatal stroke at 2 wk Benefit of 4 per 1000 (NS) Dead or dependent at 6 mo No effect (NS)Heparin IST Recurrent ischemic stroke at 2 wk Benefit of 12 per 1000 (p<0.001)5000 U bid Hemorrhagic stroke at 2 wk Harm of 3 per 1000 (p<0.05) Major extracranial hemorrhage Harm of 2 per 1000 (NS) Pulmonary embolism Benefit of 12 per 1000 (NS) Death or nonfatal stroke at 2 wk Benefit of 12 per 1000 (p<0.05) Dead or dependent at 6 mo Harm of 2 per 1000 (NS)
    86. 86. Antithrombotics for Stroke Prevention86  Primary stroke prevention  Ischemic stroke prevention  Antiplatelets: aspirin, others  Cardioembolic stroke prevention  Anticoagulants: warfarin, others  Secondary stroke prevention  Ischemic stroke prevention  Antiplatelets: aspirin, dipyridamole, ticlopidine, clopidogrel, glycoprotein IIb/IIIa receptor antagonist  Cardioembolic stroke prevention  Anticoagulants: heparin, warfarin, others
    87. 87. Decision-making of antithrombotic therapy for acute ischemic stroke87 Suspected acute No antithrombotic ischemic stroke Head CT Not completed therapy or reveals ICH Yes Eligible Administer t-PA for t-PA? Aspirin intolerance No or high risk of recurrent stroke Clopidogrel 75 mg/day Head CT ASA 160-300 mg or ASA 25 mg + at 24 hours dipyridamole 200 mg bid Rapid diagnostic evaluation Cardioembolism Large artery Small artery Arterial Cryptogenic atherothrombosis occlusion dissection ASA 100 mg/d Consider anticoagulation Consider ASA, ASA 100 mg/d Consider ASA, Warfarin, INR 2-3 If clopidogrel, or ? anticoagulation no contraindication, Extreme high risk ASA+dipyridamole Consider UFH or ? anticoagulation LMWH
    88. 88. 

    ×