1. Thrombolysing stroke in ED Dr. Ahmed AL Jabri EM, OMSB R2

2. Outlines Facts Pathophysiology of ischemic stroke . Clinical features . DDx ( worth to be mentioned ) Ix ESTABLISHING Dx of ACUTE Ischemic stroke ? Safety and efficacy of IV tPA WHOM TO THROMBOLYSE ? ( I and C/I ) TIME FRAME . ???? Local stroke team .

3. Facts 80 % of strokes are Ischemic . 20 % only of ischemic stroke will arrive to hospital within 3 hrs . 2-5% will be thrombolysed 10-15% of suspected stroke are TIAs .

4. Review and Meta-Analysis , Arch Intern Med 2007: Early Risk of Stroke After Transient Ischemic Attack Meta-analysis examined 11 observational studies that estimated the risk of stroke after a transient ischemic attack Early risk of stroke was 9.9% (95% CI 4.9%–14.9%), 13.4% (95% CI 9.8%–17.1%), and 17.3% (9.3%–25.3%) for 2, 30, and 90 days post-TIA, respectively. Facts

5. Pathophysiology The normal CBF is 40 to 60 mL/100 g of brain/min When CBF decreases to less than 15 to 18 mL/100 g of brain/min, several physiologic changes occur. The brain loses electrical activity and becomes electrically “silent,” although neuronal membrane integrity and function remain intact. Clinically the areas of the brain maintaining electrical silence manifest a neurologic deficit, even though the brain cells are viable. When CBF is less than 10 mL/100 g of brain/min, membrane failure occurs with a subsequent increase in the extracellular potassium and intracellular calcium and eventual cell death.

6. Pathophysiology ischemic penumbrais the area of the brain surrounding the primary injury, which is preserved by a tenuous supply of blood from collateral vessels. As defined by CBF, the ischemic penumbra constitutes brain tissue with blood flow of 10 to 18 mL/100 g of brain/min

7. Pathophysiology 2 Million Neurones lost every minute

8. Clinical features Presenting symptoms : be aware

10. Clinical syndromes

14. NIHSS SCORE NIHSS SCORE CAN BE PERFORMED IN 7 MINUTES . ESSENTIAL TO BE CALCULATED ( PREDICTOR OF OUTCOME AND EXCLUSION CRITERIA )

21. Structural brain lesion from tumor, hemorrhage, arteriovenous malformation or aneurysm Infection (focal abscess, septic emboli) Todd’s paralysis (neurologic deficit postseizure) Epilepsy Complicated migraine Multiple sclerosis flare Hypoglycemia Carotid dissection . Differential diagnosis of ischemic stroke

22. Syncope from any cause (especially arrhythmia) Labyrinthine disorders Benign positional vertigo (duration of vertigo <1 min), Meniere’s disease Hyperventilation/panic attack Drop attack vestibular neuronitis. Ménière's disease DDx

23. Investigations Should be individulaized ALL P.Ts Must have emergently : REFLOW ECG NCCT BRAIN

24. Investigations CBC ( PLT COUNT ) , U&E1 COAGULATION ? ECHO ? CAROTID DUPLEX ? MRI ( detect early strokes ?? Practicality )

25. NCCT BRAIN quickly differentiate an ischemic stroke from ICH and other mass lesions can identify almost all parenchymal bleeds greater than 1 cm and 95% of all subarachnoid hemorrhages ultra-early changes in ischemia includes : hyperdense artery sign (acute thrombus in a vessel), sulcal effacement, loss of the insular ribbon, loss of gray-white interface, mass effect, and acute hypodensity

26. Hyperacute Stroke: Modern Approach Aim: Revascularization of penumbra  Break down Clot! Methods: IV, IA, Mechanical Thrombolysis Most practical, with proven efficacy: IV thrombolysis with Alteplase

27. Time is Brain

28. Time is Brain : NINDS Recommended Stroke Evaluation Targets for Potential Thrombolytic Candidates

29. i.V ALTEPLASE : what is known and updates

30. Stroke Thrombolysis: Evidence for tPA < 3 Hours

36. Benefits 11-13% absolute & 30-50% reletive increase in favourable outcome at 3 months-By BI,MRS,GOS,NIHSS NNT: For every 100 patients treated with rtPA 14 avoided death or dependence Recanalization of arteries: 35%

37. Stroke Thrombolysis: Durable Benefit? 6 i.v. rtPA trials: Pooled Analysis – Benefits similar to NINDS study Dependant on adherence to Protocol. Complication rates also similar.

38. Stroke Thrombolysis: Durable Benefit? Thrombolytic therapy must be given by an experienced stroke physician after the imaging of the brain is assessed by physicians experienced in reading this imaging study2 1: Hacke W et al.: Lancet (2004) 363:768-74 2: Wahlgren N et al.: Lancet (2007) 369:275-82

39. Stroke Thrombolysis: Evidence for tPA at 3 – 4.5 hrs

40. Stroke Thrombolysis at 3-4.5 Hrs: Evidence ECASS-III Study A multicenter, randomized, placebo-controlled trial N= 821 Randomized: IV tPA v/s placebo

41. Stroke Thrombolysis at 3-4.5 Hrs Exclusion Criteria Age >80 years On oral anticoagulants regardless of INR NIHSS of >25 (Severe stroke) History of both stroke and diabetes. (Diabetes – arbitrary exclusion)

42. ECASS III – Results

43. ECASS 3 Results tPA Placebo p Favourable outcome : 52.4% 45.2% 0.04 Any ICH 27.0% 17.6% 0.001 Symptomatic ICH* 7.9% 3.5 %; 0.006 Mortality similar 7.7% 8.4% 0.68 Other serious adverse events: Similar.

44. ECASS 3: Outcome on Modified Rankin Score 0=No Sx; 6=Dead

45. Extended time window for Stroke Thrombolysis: International Guidelines AHA, European Stroke Intiative, UK-NICE recommended Eligible patients who can be treated 3 to 4.5 hours after onset of stroke symptoms should receive tPA. AHA: Class I recommendation, level B. EUSI: Class I, Level A

49. May be used in patients with seizures at stroke onset, if the neurological deficit is related to acute cerebral ischaemia .

52. Possible subarachnoid hemorrhage

53. Arteriovenous malformation

54. Seizure with postictal residual neurologic impairmentSystolic BP >185 mm Hg or DBP >110 mm Hg despite repeated measurements and treatment. Platelets <100,000/mm3 PT >15 or INR >1.7 Active internal bleeding or acute trauma (fracture)

55. Contraindications for alteplase Relative CI Suspected acute pericarditis Rapidly improving stroke symptoms MI with in 3 mo Glucose level <3.5 mM or > 22 mM/l Head trauma or stroke in the previous 3 months Arterial puncture at a noncompressible site within 1 week

56. Post –tPA management Close observation in ICU for 24 hr Monitor: BP, Sensorium, Vitals for e/o: Hypertension, ICH, Systemic hemorrhage. Serial BP at 15 min to 1 hr intervals BP goal of <180/115 mm Hg. In case of higher BP: IV Labetalol, Nicardepine

57. If intracranial hemorrhage present: Obtain fibrinogen results. Prepare for administration of 6 to 8 units of cryoprecipitate containing factor VIII. Prepare for administration of 6 to 8 units of platelets. Consider alerting and consulting a hematologist or neurosurgeon. Consider decision regarding further medical and/or surgical therapy. Consider second CT to assess progression of intracranial hemorrhage. A plan for access to emergent neurosurgical consultation is highly recommended.

58. Putting it all together

59. Pre - hospital

60. Our protocol Age 18-80 Clinical diagnosis of a stroke causing a measurable neurological difference Time of symptom onset is known Sufficient time in 3 hour therapeutic window to assess and treat patient No clear contra-indications to thrombolysis

61. Our protocol Contra-indications Intracranial haemorrhage on CT scan > 3 hours since onset of stroke Improving symptoms Seizure at onset Bleeding disorder Active cancer

62. Relative contra-indications Age <18 and >80 Warfarin Rx with INR >1.6 NIHSS <4 or > 25 CT showing early ischaemic change

63. Putting it all together! spouse nurse paramedic BP + RBS arrange clinical venflon CTscan assessment bloods porter DOCTOR-PATIENT relatives arrange assent/consent bed NIHSScore weight/dose BP (again) read CT scan start drug

64. Qs, COMMENTS