Acute ischemic stroke

This includes scores, prehospital and emergency department management of stroke. it goes into details of stabilisation and general management. definitive management options are thrombolysis or thrombectomy. briefly described complications of stroke and management as well

1. Acute ischemic STROKE MANAGEMENT DR KTD Priyadarshani Registrar in emergency medicine Teaching hospital- Peradeniya

2. OUTLINE Introduction Scores used in stroke Prehospital care ED management Stabilization & General management Definitive Management options Complications of stroke

3. INTRODUCTION

4. Definition The World Health Organization rapidly developing clinical signs of focal (or global) disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin 11% of all deaths Significant cause of morbidity

5. Classification Ischemic (85%) Hemorrhagic Unable to distinguish between a hemorrhagic and ischemic stroke until imaging obtained

6. ETIOLOGY Embolism Cardiac- MI, AF, Valvular disease, PFO Non cardiac- air embolism Thrombosis Atherosclerosis Prothrombotic states Perfusion failure & artery to artery embolism Large artery atheromatous plaque Vasculitis

7. STOKE SYNDROMES Contralateral leg> face & arm Contralateral Face & arm > leg Lateral medullary Syndrome/ Wallenberg syndrome

8. STROKE SCORES

9. FAST- ED (field assessment stroke triage for emergency destination)

10. BE FAST

11. RACE SCORE

12. LAMS ( los angeles motor scale)

13. NIHSS Score 11 Components Level of consciousness Gaze Visual fields Facial movements Motor function Limb ataxia Sensory Language Articulation Extinction or inattention Scores range from 0 (no deficit) to 42 Classification Mild 0-4 Moderate 4-24 Severe >25

14. NIHSS Score reproducibly and quantifiably assess a patient’s stroke symptoms. Limited use in in scoring brainstem strokes estimating the severity of a right hemispheric stroke. A low score is not an absolute contraindication and potential risks should be weighed against anticipated benefits.

15. ASPECT score (Alberta stroke program early CT score)

16. ROSIER score 7 point scoring system Sensitivity 83-97% Specificity 18-93%

17. STROKE MIMICS Mimic Clinical features Seizure (17%) Systemic infection (17%) Systemic symptoms Brain tumor (15%) Gradual onset Toxic- metabolic disorders (13%) Hyponatremia Hypoglycemia/ hyperglycemia Drug overdose Bed side glucose Serum electrolytes VBG Positional vertigo (6%) Past episodes & reproducible Migraine with aura Aura, headache Head injury Hx

18. PREHOSPITAL CARE

19. Initial prehospital evaluation History and physical examination Determine LKW ABCs Glucose check Stroke severity screen exam Obtain IV access and blood for IX Contact stroke center and pre hospital notification

20. Stroke patients are dispatched at the highest level of care available in the shortest time possible.

21. ED MANAGEMENT

22. ED- Evaluation Activate stroke code system Vital signs Maintain oxygen saturation >94% Determine time of onset/ LKW Determine NIHSS score CT/CTA Medication list (Anticoagulants) IV access (18G) IX- CBS, FBC with platelets, PT/INR, PTT, ECG, troponin baseline, CXR

23. NCCT BRAIN EARLY SIGNS OF ACUTE INFARCTION

24. DENSE MCA SIGN

25. DOT SIGN- VARIANT OF DENSE MCA

26. INSULAR RIBBON SIGN

27. BASAL GANGLIA ASYMMETRY

28. LOSS OF GRAY WHITE MATTER INTERFACE

29. LOW ATTENUATION OF THE CORTEX

30. STABILISATION & GENERAL MANAGEMENT

31. AIRWAY, BREATHING & OXYGENATION Airway support and ventilatory support Low GCS Bulbar dysfunction SpO2 > 94% Hyperbaric oxygen- when AIS caused by air embolism

32. BP CONTROL Maintain normotension and euvolemia . If the patient is a potential thrombolysis candidate, interventions to control BP should be initiated immediately. Target BP goal for patients eligible for IV tPA is <185/110  mmHg On ce IV  tPA is initiated, BP must be maintained below 180/105  mmHg for 24  h For mechanical thrombectomy BP < 185/110 mmHg If thrombolysis or thrombectomy is not practiced BP >220/120 target 15% reduction in first 24 hrs Drug induced hypertension- not well established.

33. DRUG DOSE Labetalol IV 10-20 mg over 1-2 min, may repeat once Nicardipine IV 5mg/h, titrate up by 2.5mg/h every 5-15 min Max 15 mg/ hr Clevidipine IV 1-2 mg/ hr , titrate by doubling the dose every 2-5 min Max 21 mg/ hr Hydralazine IV 10-20 mg IV every 4-6 hr Clonidine O 0.1- 0.2 mg hourly 0.05- 0.1 mg Total dose 0.3mg Sodium nitroprusside 0.3-0.5 mcg/kg/min initially, increase by 0.5 mcg/ kg/ min every few min

34. SBP > 180-230 mmHg or BDP >105-120 mmHg DRUG DOSE Labetalol IV 10mg bolus 2-8 mg/min infusion Nicardipine IV 5 mg/h titrate up 2.5mg/h every 5-15 min, maximum 15mg/ hr Clevidipine IV 1-2 mg/ hr Titrate up by doubling dose every 2-5min until desired BP reached, maximum 21 mg/ hr

35. IV Fluid Hypovolemia may exacerbate ischemic brain edema and increase stress on the myocardium.  Stroke patients should receive maintenance isotonic intravenous fluids in the form of normal saline.  The utilization of plasma volume expanders has not demonstrated benefit. High dose of albumin- not recommended

36. TEMPERATURE Hyperthermia >38℃ - Identify and treat Antipyretics Antibiotics if infection+ Effect of induced hypothermia- uncertain

37. BLOOD GLUCOSE Hypoglycemia <60 mg/ dL Treat Persistent inhospital hyperglycemia during 24 hrs - worsen outcome Target 140-180mg/ dL

38. DEFINITIVE MANAGEMENT

39. Definitive management options Thrombolysis- IVT Thrombectomy- EVT, IVR Conservative

40. THROMBOLYSIS Benefit of therapy is time dependent Prepare to treat potential adverse effects Informed written consent- risk vs benefit Do not wait for lab reports If abnormality in clotting profile detected (INR>1.7 or PT is abnormally elevated, platelet count <100,000 mm3 ), then thrombolytics should be discontinued.

41. Thrombolysis- Eligibility criteria Ischemic stroke symptoms causing measurable neurological deficit onset < 3 hrs Patient is > 18 yrs of age 3- 4.5 hrs <80 yrs +/- No DM, no prior stroke NIHSS <25 Not taking any oral anticoagulants No imaging evidence of ischemic injury involving more than 1/3 of MCA territory

42. Thrombolysis- Exclusion criteria Major head trauma, ischemic stroke, intracranial/ spinal surgery in previous 3M History of ICH or intracerebral neoplasm Signs and symptoms suggestive of subarachnoid hemorrhage, infective endocarditis, or aortic arch dissection GI malignancy or recent bleeding with in 21 days Coagulopathy ( Plt <100, INR >1.7, aPTT >40s, PT>15) LMWH within 24h Taking direct thrombin inhibitors or direct factor Xa inhibitors APTT, INR, Platelet count, ecarin clotting time, TT, direct factor Xa activity assays are Normal Has not taken dose for > 48 hrs with normal renal function CT shows severe hypoattenuation, hypodensity > 1/3 of cerebral hemisphere or ICH

43. ADDITIONAL RECOMMENDATIONS Unknown time of onset (wakeup stroke)- DWMRI lesion < 1/3 of MCA territory, no visible signal change on FLAIR Early improvement- if impairment + Preexisting disability, Preexisting dementia Consider quality of life vs risk Life expectancy Seizure at onset- recommended if residual impairment is secondary to stroke Blood glucose- normalize

44. Bleeding risk Warfarin with INR <1.7, PT < 15 sec Hx of bleeding diathesis or coagulopathy- unknown safety and efficacy Arterial puncture of non compressible blood vessel in 7D- uncertain Major trauma, Surgery with in 14 D not involving head- consider carefully Menstruation No menorrhagia- warn risk of increase menstrual flow Menorrhagia hx or active causing anemia- consult gynecologist Menorrhagia without anemia- risk vs benefit GI and GU Bleeding- low bleeding risk Concomitant tirofiban, epifibatide - not well established Malignancy Extra cranial neoplasms- probably recommended Systemic malignancy Life expectancy > 6M No coagulation abnormality, recent surgey , systemic bleeding

45. CVS Conditions Extracranial cervical arterial dissection- safe within 4.5h Intracranial arterial dissection- uncertain Acute MI- IV alteplase dose for cerebral ischemia followed by PCI and steniting Recent MI- 3M NSTEMI, STEMI Rt or inferior myocardium- - recommended STEMI Left anterior myocardium- reasonable Acute pericarditis- Urgent consultation with a cardiologist LA or LV thrombus- Major AIS- reasonable Procedural stroke (cardiac or cerebral angiography)- usual eligibility criteria Pregnancy Risk of uterine bleeding- risk vs benefit Early post partum <14 D- not well established Illicit drug use- reasonable Stroke mimic Risk of symptomatic ICH is quite low Alteplase is recommended over delaying to pursue additional diagnostic studies

46. Neuro conditions Lumbar dual puncture preceding 7D- may consider Unruptured intracranial aneurysm (<10 mm)- probably recommended Giant unruptured and unsecured- uncertain Intracranial vascular malformations- Unruptured and untreated- high risk of ICH Cerebral microbleeds- 1-10 in MRI- reasonable >10- increased risk of ICH Ophthalmological conditions- Diabetic hemorrhagic retinopathy, other hemorrhagic ophthalmic conditions- risk of visual loss

47. Thrombolysis – informed consent Current condition Definitive management option- thrombolysis or thrombectomy Expectation- 30% chance of independent function after 3 months according to meta analysis. Immediate improvement is not expected Major complications Angioedema- specially on pt with ACEI ICH 5-7%

48. Thrombolysis- IV ALTEPLASE 2 peripheral IV lines Calculate actual body weight 0.9 mg/kg (max 90mg) 10% given in bolus over 1 st minute Rest given over 1 hour infusion Stop immediately if neurological deterioration Improves chance of recovery without significant disability at 90 days from 26% to 39% if given with in 3 hrs

49. Thrombolysis- procedure BP and neurological assessment every 15  min for the first 2 h after starting alteplase , every 30 min for the next 6 h, hourly for the next 16 h . While the half-life of alteplase is approximately 5 min , and only 20% of the medication is still present and active at 10 min after completion of the infusion, PT and activated partial thromboplastin time (APTT) are prolonged and fibrinogen levels are decreased for 24 h or more. 

50. Thrombolysis complications- ICH 50% or greater mortality rate. This is often accompanied by a marked rise in blood pressure (BP); however, a marked rise or fall in BP alone may signal an ICH. Signs Worsening of GCS/ Neurology Worsening of NIBP Severe headache New nausea & vomiting Pupillary inequality

51. Thrombolysis complications- ICH Stop alteplase infusion Obtain a non-contrast head CT scan STAT  Obtain CBC, PT, PTT, INR, fibrinogen level, type and cross-match  Vital signs every 15  min (neurological assessment for signs of increased intracranial pressure). Assess GCS/pupil response. Treat BP and use noninvasive interventions to lower intracranial pressure (ICP) (raise the head of bed, neck midline)  Supportive therapy, including management of BP, ICP, cerebral perfusion pressure (CPP), temperature, and glucose should be performed.  Consult neurosurgery .   For small, asymptomatic, hemorrhagic conversion, conservative medical management may be considered after weighing the risks and benefits of reversal agents. 

52. Reversal of effects of Alteplase DRUG DOSE Cryoprecipitate (contains fibrinogen ) Onset in 1hr Peak in 12 hr 10 units infused over 10–30  min administer additional dose for fibrinogen level <150  mg/dl. Antifibrinolytics Tranexamic acid 1000  mg (10–15  mg/kg) IV ε- aminocaproic acid Peak in 3h 4–5  g IV over 1  h, followed by 1  g IV until bleeding is controlled. platelets One bag of single donor platelets 6–8 bags of random donor platelets

53. Thrombolysis complications- Orolingual angioedema Maintain airway Intubation if edema involve larynx, palate, floor of mouth or orpharynx with rapid progression (with in 30 min) Awake fiberoptic intubation Nasal intubation, tracheostomy- bleeding risk Discontinue IV alteplase infusion and hold ACEI Administer IV Methylprednisolone 125mg IV diphenhydramine 50 mg IV ranitidine 50mg or famotidine 20 mg Further increase angioedema- epinephrine 0.1% S/C 0.3mL or nebulizer 0.5ml Icatibant - selective bradykinin b2 receptor antagonist plasma derived C1 esterase inhibitor

54. Trials of thrombolysis NINDS A & B Trial- Benefit of IV alteplase in acute stroke 3 hrs from LKW ECASS III Trial Efficay of thrombolysis from 3-4.5 h WAKE- UP Trial Benefit of alteplase based on favorable perfusion studies for patients who wakeup with symptoms EXTEND trial Benefit from 4.5-9 hrs based on perfusion studies

55. ENDOVASCULAR TREATMENT If eligible for IV alteplase - proceed with thrombolysis No assessment for clinical response post thrombolysis

56. STENT RETREIVER Eligibility criteria Functionally independent prestroke Causative occlusion of the internal carotid artery or MCA segment1 (M1) Age >18 yrs NIHSS >6 ASPECTS >6 Treatment can be initiated with in 6hrs (groin puncture)

57. 6-24 hr time window Based on presence of target mismatch profile in CR/MR perfusion imaging Based on the results of the DAWN and DEFUSE 3 trials , it is recommended that in patients presenting with an AIS within 6–24  h of LKW time who have an LVO in the anterior circulation, obtaining a CTP, DWI— MRI+MRI perfusion is recommended to aid in selection of patients for mechanical thrombectomy who meet the eligibility criteria. 

58. Antiplatelet and anticoagulant Aspirin 24-48 hrs after onset IV alteplase - delay 24hrs later But continue if withholding causes substantial risk Non carioembolic minor stroke + not thrombolysed DAPT with in 24 hrs - 21 days Avoid concomitant abciximab, IV aspirin with in 90 min of start of alteplase No anticoagulant use is recommended

59. COMPLICATIONS OF STROKE

60. Cerebral edema Large territorial cerebral and cerebellar infarction Use of brief moderate hyperventilation (pco2 target 30-34 mmHg) Hypothermia/ barbiturates- not recommended Corticosteroids not recommended- increases risk of infections

61. Cerebral edema- clinical features EARLY LATE Headache Changes in level of consciousness or reduction in GCS or FOUR score >2 points Irritability, Seizure Ipsilateral change in pupillary size, shape and light responsiveness Vomiting Contralesionally hemiparesis (new or worsening) Photophobia, nystagmus, diplopia Contralesionally change in pupillary size and ipsilesional hemiparesis ( Kernohan’s phenomenon) Lethargy Cushing's triad

62. Hyperosmolar therapy Mannitol IV 0.5-1 g/kg bolus through peripheral IV line over 5-15 min repeated every 4-6 hrs Decide on repeat dosing with osmolar gap No therapeutic benefit if osmolar gap >20 mOsm /kg HTS 2-23.4% >7.5% in central line Serum Na every 4-6 hrs Na target <160 mEq /L

63. Seizures In 2-23% of patients within the first days after AIS A fraction would develop chronic seizure disorder Use antiepileptics as seizure occur with other acute neurological conditions Prophylactic use- not recommendd

64. Hemorrhagic transformation In 5% of uncomplicated ischemic stroke in the absence of fibrinolytic Rx With in 2-14 days- usually with in 1 st week More likely to occur with larger infarct volumes Initiation or continuation of antiplatelet or anticoagulation considered depending on specific clinical scenario

65. References American Heart Association 2019 American stroke association Guidelines

66. QUESTIONS?

67. Thank you!