1. Stroke 2006 Stroke 2006: Optimal ED Patient Management Strategies Case Studies to Challenge the Experts

2. Stroke 2006 New York ACEP Scientific Assembly Lake George, NY July 5-7, 2006

3. Stroke 2006 Thank you to AstraZeneca for their support of this stroke educational meeting

4. Stroke 2006 Panelists Andy Jagoda, MD, FACEP Andy Jagoda, MD, FACEP Mount Sinai School of Medicine Peter L. Shearer, MD, FACEP Peter L. Shearer, MD, FACEP Mount Sinai School of Medicine Mount Sinai School of Medicine Edward P. Sloan, MD, MPH, FACEP University of Illinois at Chicago Edward P. Sloan, MD, MPH, FACEP University of Illinois at Chicago

5. Stroke 2006 Disclosures Andy Jagoda, MD Andy Jagoda, MD AstraZeneca, FERNE AstraZeneca, FERNE Peter L. Shearer, MD, FACEP Peter L. Shearer, MD, FACEP None None Edward P. Sloan, MD, MPH Edward P. Sloan, MD, MPH FERNE FERNE

6. Stroke 2006 Prior Panelists Andy Jagoda, MD, FACEP (Moderator) Mount Sinai School of Medicine Andy Jagoda, MD, FACEP (Moderator) Mount Sinai School of Medicine Thomas G. Brott, MD Mayo Clinic Jacksonville Thomas G. Brott, MD Mayo Clinic Jacksonville E. Bradshaw Bunney, MD, FACEP University of Illinois at Chicago E. Bradshaw Bunney, MD, FACEP University of Illinois at Chicago J. Stephen Huff, MD, FACEP University of Virginia J. Stephen Huff, MD, FACEP University of Virginia Edward P. Sloan, MD, MPH, FACEP University of Illinois at Chicago Edward P. Sloan, MD, MPH, FACEP University of Illinois at Chicago

7. Stroke 2006 Prior Panelists’ Disclosures Andy Jagoda, MD Andy Jagoda, MD AstraZeneca AstraZeneca Thomas G. Brott, MD Thomas G. Brott, MD None None E. Bradshaw Bunney, MD E. Bradshaw Bunney, MD AstraZeneca, Genentech consultant AstraZeneca, Genentech consultant J. Stephen Huff, MD J. Stephen Huff, MD None None Edward P. Sloan, MD, MPH Edward P. Sloan, MD, MPH None None

8. Stroke 2006 Global Objectives Improve acute stroke patient care Improve acute stroke patient care Minimize morbidity and mortality Minimize morbidity and mortality Expedite disposition Expedite disposition Optimize resource utilization Optimize resource utilization Enhance our job satisfaction Enhance our job satisfaction

9. Stroke 2006 Session Activities Present a relevant clinical case Present a relevant clinical case Poll the audience about care Poll the audience about care Discuss the questions Discuss the questions Understand areas of consensus Understand areas of consensus Explore areas of uncertainty Explore areas of uncertainty Go forth and prosper Go forth and prosper

10. Stroke 2006 Case Presentation 62 year-old professor has an apparent stroke while teaching at the local community college.62 year-old professor has an apparent stroke while teaching at the local community college. Contact to the local EMS base station occurs within 15 minutes of the onset of symptoms.Contact to the local EMS base station occurs within 15 minutes of the onset of symptoms. He arrives at the closest ED within 30 minutes of symptom onset.He arrives at the closest ED within 30 minutes of symptom onset.

11. Stroke 2006 Case Presentation VS 178/80 RR 18 P 96 Temp 98.6VS 178/80 RR 18 P 96 Temp 98.6 Cardiopulmonary exam OKCardiopulmonary exam OK Mental Status OKMental Status OK Neurological ExamNeurological Exam Awake and alertAwake and alert R facial weaknessR facial weakness Slurred speechSlurred speech Right visual field neglectRight visual field neglect Unable to purposefully move RUE / RLEUnable to purposefully move RUE / RLE

12. Stroke 2006 Question: TIA ED Visit Had this patient presented to the ED two weeks earlier with dizziness and numbness in his R upper extremity, what would be your approach?

13. Stroke 2006 Question: TIA ED Visit A. A. I admit all TIA patients regardless of the severity of the symptoms.

14. Stroke 2006 Question: TIA ED Visit B. I only admit those patients who have clear motor weakness or visual symptoms (amaurosis fugax) because of a greater stroke risk.

15. Stroke 2006 Question: TIA ED Visit C. I might consider sending this patient home, but only if I have completed a cranial CE and an evaluation of the carotids (Doppler, CTA, MRA).

16. Stroke 2006 Question: TIA ED Visit D. I would send this patient home with aspirin therapy and arrange that a physician complete a TIA work-up as an outpatient.

17. Stroke 2006 Question: TIA ED Visit E. I don’t really have an opinion on what to do with this TIA patient, and so would depend on my neurologist for a disposition decision.

18. Stroke 2006 Question: TIA ED Visit A. A. I admit all TIA patients. B. B. I only admit those patients who have clear motor weakness or visual symptoms. C. C. Send home after a cranial CT and a carotid evaluation. D. D. Send home, outpatient TIA workup. E. E. No opinion, ask the neurologist.

19. Stroke 2006 Question: EMS Triage Regarding EMS triage, should this patient be:

20. Stroke 2006 Question: EMS Triage A. A.Transported to the closest hospital?

21. Stroke 2006 Question: EMS Triage B. Diverted to the closest primary stroke center?

22. Stroke 2006 Question: EMS Triage C. Diverted to the closest tertiary center with 24/7 interventional radiology?

23. Stroke 2006 Question: EMS Triage D. Diverted to the closest comprehensive stroke center?

24. Stroke 2006 Question: EMS Triage E. Asked to finish his class first?

25. Stroke 2006 Question: EMS Triage A. A.Closest hospital B. B.Closest primary stroke center C. C.Closest 24/7 IR tertiary center D. D.Closest comprehensive stroke center E. E.Asked to finish the class first

26. Stroke 2006 Question: Inter-hospital Transfer If this patient is transported to the closest ED of a hospital with no specific stroke team or protocol, which of the following best describes circumstances when transfer to a tertiary or stroke center should take place for this stroke patient?

27. Stroke 2006 Question: Inter-hospital Transfer A. A. There are no indications for inter-hospital transfer to take place.

28. Stroke 2006 Question: Inter-hospital Transfer B. B. The patient should be transferred after IV tPA is administered.

29. Stroke 2006 Question: Inter-hospital Transfer C. C. Transfer should take place only if IV tPA is not indicated and CNS intra-arterial thrombolytic therapy or thrombus removal is likely.

30. Stroke 2006 Question: Inter-hospital Transfer D. Transfer should take place for all patients if the time from symptom onset is between three and ten hours in order to allow advanced diagnostics to be provided acutely.

31. Stroke 2006 Question: Inter-hospital Transfer E. Transfer to a primary stroke center should take place for all stroke patients, regardless of the time of symptom onset, whether IV tPA has been provided, and whether an acute clot intervention is contemplated

32. Stroke 2006 Question: Inter-hospital Transfer F. I have no idea when inter- hospital transfer should take place for patients such as this one.

33. Stroke 2006 Question: Inter-hospital Transfer A. A.No indications B. B.After IV tPA is administered. C. C.IV tPA is not indicated and CNS intra-arterial thrombolytic therapy or thrombus removal is likely D.Symptoms 3-10 hours, diagnostics E.Transfer all stroke patients F.I have no idea

34. Stroke 2006 Cincinnati Prehospital Stroke Scale One positive = possible stroke

35. Stroke 2006 11 elements of a Primary Stroke Center JAMA 2000; 283:3102-3109 EMS integrated into the acute stroke response EMS integrated into the acute stroke response Stroke team available 24 / 7 Stroke team available 24 / 7 Written care protocols Written care protocols ED integrated into the acute stroke team ED integrated into the acute stroke team Stroke unit Stroke unit Neurosurgical services available within 2 hours Neurosurgical services available within 2 hours Commitment from the institution Commitment from the institution Neuroimaging interpreted within 45 min of arrival Neuroimaging interpreted within 45 min of arrival Laboratory services with rapid turn around of tests Laboratory services with rapid turn around of tests CQI program including a database or registry CQI program including a database or registry Continuing education program Continuing education program

36. Stroke 2006 NINDS Symposium 2002: Improving the Chain of Recovery for Acute Stroke in Your Community ED – basic ED – basic Recognizes that not all EDs can provide thrombolytic care Recognizes that not all EDs can provide thrombolytic care Stabilization: ABC / BP / glucose / temp Stabilization: ABC / BP / glucose / temp Transfer protocols Transfer protocols Primary Stroke Center Primary Stroke Center Comprehensive Stroke Center Comprehensive Stroke Center Tertiary care center Tertiary care center Advanced stroke expertise in neuroimaging, neurosurgery, interventional neuro-radiology Advanced stroke expertise in neuroimaging, neurosurgery, interventional neuro-radiology

37. Stroke 2006 Stroke Centers Improves outcomes? Improves outcomes?  Newell et al. clinical efficiency tools improve stroke management in a rural southern health system. Stroke 1998; 29:1092-1098  Wentworth et al. Implementation of an acute stroke program decreases hospitalization cost and length of stay. Stroke 1996; 27:1040-1043.  Douglas et al. Do the brain attach coalition’s criteria for stroke centers improve care for ischemic stroke? Neurology 2005; 64: 422-427  Implementation increased incidence of t-PA use

38. Stroke 2006 AHRQ #127: Acute Stroke Are designated centers effective in reducing stroke related disability and mortality? Are designated centers effective in reducing stroke related disability and mortality? No studies were identified No studies were identified Studies have shown that stroke teams decrease the time to evaluation Studies have shown that stroke teams decrease the time to evaluation Lattimore et al showed that creation of stroke team increased tPA use from 1.5% to 10.5% of acute stroke patients seen Lattimore et al showed that creation of stroke team increased tPA use from 1.5% to 10.5% of acute stroke patients seen

39. Stroke 2006 IV tPA Utilization Cleveland Clinic Health System July 1997 - June 1998 70 pts treated with IV tPA: 1.8% ischemic strokes 1.8% ischemic strokes 11.1% of ischemic strokes arriving < 3 hrs 11.1% of ischemic strokes arriving < 3 hrs 31% selected protocol deviations 16% symptomatic intracranial hemorrhage intracranial hemorrhage July 1999 - June 2000 53 pts treated with IV tPA: 2.4% ischemic strokes 2.4% ischemic strokes 23.4% of ischemic strokes arriving < 3 hrs (53/226) 17% selected protocol deviations 6.5% symptomatic 6.5% symptomatic intracranial hemorrhage intracranial hemorrhage Katzan et al, Stroke 2003;34:799-800

40. Stroke 2006 JCAHO Disease Specific Care Certification Joint initiative between ASA and JCAHO Joint initiative between ASA and JCAHO Voluntary participation Voluntary participation 94 accredited hospitals 94 accredited hospitals 36 site visits in progress 36 site visits in progress 718 applications pending 718 applications pending Premise is that accreditation process will drive quality measures and improve outcomes Premise is that accreditation process will drive quality measures and improve outcomes No emergency medicine society has endorsed this initiative No emergency medicine society has endorsed this initiative t-PA controversy t-PA controversy Overcrowding Overcrowding Medical legal implications Medical legal implications

41. Stroke 2006 Question: Use of the NIHSS Which of the following describes your views regarding the use of the NIHSS in evaluating stroke severity and the indications for various stroke therapies?

42. Stroke 2006 Question: Use of the NIHSS A. A. Every emergency physician should know how to calculate the NIHSS for patients such as this one, since it is the standard of care for determining stroke severity and the need for any and all stroke therapies.

43. Stroke 2006 Question: Use of the NIHSS B. It is obvious how severe this patient’s stroke is, and the need for all potential stroke therapies can be determined clinically without actually calculating the NIHSS.

44. Stroke 2006 Question: Use of the NIHSS C. The NIHSS can be reliably estimated by determining symptom severity in four categories: motor, speech, mental status, and visual/neglect.

45. Stroke 2006 Question: Use of the NIHSS D. The NIHSS is a research tool that can be calculated retrospectively as needed as long as the neurological exam in the ED is documented appropriately.

46. Stroke 2006 Question: Use of the NIHSS E. When I am considering IV tPA, I just quickly calculate the NIHSS using Internet tools.

47. Stroke 2006 Question: Use of the NIHSS F. What does NIHSS stand for, anyways?

48. Stroke 2006 Question: Use of the NIHSS A. A.NIHSS is the standard of care B. B.Determine Rx clinically, no NIHSS C. C.Estimate NIHSS in 4 clinical areas D.Calculate retrospectively from exam E.Quickly calculate NIHSS with Internet F.What does NIHSS stand for?

49. Stroke 2006 Question: Patient NIHSS What is the approximate NIHSS of this patient?What is the approximate NIHSS of this patient?  Awake and alert  R facial weakness  Slurred speech  Right visual field neglect  Unable to purposefully move his RUE / RLE

50. Stroke 2006 Question: Patient NIHSS A. A.0-5 B. B.5-10 C. C.10-15 D.15-20 E.Greater than 20

51. Stroke 2006 Question: Use of Scales Regarding the use of stroke outcome scales such as the Modified Rankin Scale (MRS) or the Barthel Index (BI), which of the following is your clinical approach?Regarding the use of stroke outcome scales such as the Modified Rankin Scale (MRS) or the Barthel Index (BI), which of the following is your clinical approach?

52. Stroke 2006 Question: Use of Scales A. I use these scales in assessing stroke patient severity in the ED.

53. Stroke 2006 Question: Use of Scales B. I understand the MRS and the BI, and I use them to help in assessing the effectiveness of new stroke therapies from published clinical trials.

54. Stroke 2006 Question: Use of Scales C. I do not have any idea how these outcome scales are utilized, either in the ED or after hospital disposition.

55. Stroke 2006 Question: Use of Scales D. These scales correlate with the NIHSS, making their use superfluous.

56. Stroke 2006 Question: Use of Scales E. I have not ever heard of these scales, let alone use them!

57. Stroke 2006 Question: Use of Scales A. A.I use these scales in the ED B.Scales assess the effectiveness of new stroke therapies C.No idea how these outcome scales are utilized D.Scales correlate with the NIHSS, making their use superfluous E.I have never heard of these stroke scales

58. Stroke 2006 The utility of clinical scales Allow gross quantification of injury/pathology Allow gross quantification of injury/pathology Aid in communication to consultants Aid in communication to consultants Can be used to track improvement or deterioration in the acute treatment phase Can be used to track improvement or deterioration in the acute treatment phase Can be used to track outcome Can be used to track outcome Can be useful research tools Can be useful research tools Adapted from slide set of Kama Guluma, MD

59. Stroke 2006 The NIH Stroke Scale Adapted from slide set of Kama Guluma, MD

60. Stroke 2006 The Stroke-focused Neuro Exam The NIHSS 1. Level of consciousness 2. Gaze 3. Visual fields 4. Facial strength 5. Arm strength 6. Leg strength 7. Limb ataxia (FNF, heel-down-shin) 8. Sensation (pinch/pinprick) 9. Language (re: aphasia) 10. Dysarthria 11. Extinction/inattention (bilat sensory) Maximum Score = 42 Maximum score from ischemic stroke = 31

61. Stroke 2006 The NIH Stroke Scale LEVEL OF CONSCIOUSNESS

62. Stroke 2006 The NIH Stroke Scale GAZE VISUAL FIELDS

63. Stroke 2006 The NIH Stroke Scale FACIAL MOTOR

64. Stroke 2006 The NIH Stroke Scale MOTOR OF THE ARM MOTOR OF THE LEG ATAXIA

65. Stroke 2006 The NIH Stroke Scale SENSORY

66. Stroke 2006 The NIH Stroke Scale LANGUAGE

67. Stroke 2006 The NIH Stroke Scale DYSARTHRIA

68. Stroke 2006 The NIH Stroke Scale EXTINCTION/NEGLECT

69. Stroke 2006 What the NIHSS score means to the EP NIHSS 1 - 4: mild stroke NIHSS 1 - 4: mild stroke NIHSS 5 -15: moderate stroke NIHSS 5 -15: moderate stroke NIHSS 15 – 20: moderate to severe stroke NIHSS 15 – 20: moderate to severe stroke NIHSS > 20: severe stroke NIHSS > 20: severe stroke Prognosis: likelihood of favorable outcome Prognosis: likelihood of favorable outcome NIHSS < 10: 60 – 70% NIHSS < 10: 60 – 70% NIHSS > 20: 4 -16% NIHSS > 20: 4 -16%

70. Stroke 2006 What the NIHSS score means to the EP Chance of ICH with tPA Chance of ICH with tPA NIHSS < 10: 3% NIHSS < 10: 3% NIHSS > 20: 17% NIHSS > 20: 17% Stroke. 2003;34:1056 –1083. Ann Emerg Med. 2001;37:202-216

71. Stroke 2006 Consideration: the “low NIHSS score” stroke with a devastating effect on livelihood

72. Stroke 2006

73. Functional Outcome Scales Modified Rankin scale (mRS) Modified Rankin scale (mRS) Barthel Index (BI) Barthel Index (BI) Glasgow Outcome Scale (GOS) Glasgow Outcome Scale (GOS) Utilize scored assessments of patient’s functional status Utilize scored assessments of patient’s functional status Can be used to gauge: Can be used to gauge: pre-morbid baseline pre-morbid baseline outcome outcome

74. Stroke 2006 ScoreDescription 6Dead 5 Severe disability: bedridden, incontinent, and requiring constant nursing care and attention 4 Moderately severe disability: unable to walk without assistance and unable to attend to own bodily needs without assistance 3 Moderate disability: requiring some help, but able to walk without assistance 2 Slight disability: unable to carry out all previous activities, but able to look after own affairs without assistance 1 No significant disability: despite symptoms, able to carry out all usual duties and activities 0 No symptoms at all Modified Rankin Scale Good outcome = score of 0 - 1

75. Stroke 2006 Barthel Index Feeding 0 = unable 5 = needs help cutting, spreading butter, etc, or requires modified diet 10 = independent Bathing 0 = dependent 5 = independent (or in shower) Grooming 0 = needs help with personal care 5 = independent face/hair/teeth/shaving (implements provided) Dressing 0 = dependent 5 = needs help but can do about half unaided 10 = independent (including buttons, zips, laces, etc) Bowels 0 = incontinent (or needs enemas) 5 = occasional accident 10 = continent

76. Stroke 2006 Barthel Index Bladder 0 = incontinent, or catheterized and unable to manage alone 5 = occasional accident 10 = continent Toilet use 0 = dependent 5 = needs some help but can do something alone 10 = independent (on and off, dressing, wiping) Transfers (bed to chair and back) 0 = unable, no sitting balance 5 = major help (1 or 2 people, physical), can sit 10 = minor help (verbal or physical) 15 = independent Mobility (on level surfaces) 0 = immobile or <50 yards 5 = wheelchair-independent, including corners, >50 yards 10 = walks with help of 1 person (verbal or physical) >50 yards 15 = independent (but may use any aid—eg, stick) >50 yards Stairs 0 = unable 5 = needs help (verbal, physical, carrying aid) 10 = independent 100 point scale; good outcome = 95 - 100

77. Stroke 2006 ScoreDescription 1DEAD 2 VEGETATIVE STATE Unable to interact with environment; unresponsive 3 SEVERE DISABILITY Able to follow commands/ unable to live independently 4 MODERATE DISABILITY Able to live independently; unable to return to work or school 5 GOOD RECOVERY Able to return to work or school Glasgow Outcome Scale

78. Stroke 2006 Functional Scales and tPA Outcome NINDS tPA trial: NINDS tPA trial: 13% absolute increase in mRS 0 – 1 in treatment group 13% absolute increase in mRS 0 – 1 in treatment group 12% increase in BI 95-100 in treatment group 12% increase in BI 95-100 in treatment group Means: 9 patients need to be treated for one improvement in outcome (NNT = 9) Means: 9 patients need to be treated for one improvement in outcome (NNT = 9)

79. Stroke 2006 1-Year Outcome in NINDS trial Barthel Index Modified Rankin Scale Glasgow Outcome Scale Kwiatkowski TG, et al. N Engl J Med. 1999;340:1781-1787.

80. Stroke 2006 Looking at NINDS data more closely The sliding scale dichotomy endpoint Saver J, 31 st International Stroke Conference, Kissimmee, FL, Feb 2006 mRS: 0 1 2 3 4 5 6 Baseline-adjusted severity endpoint reanalysis, 3-month outcome NIHSS 0-7 “GOOD” NIHSS 8-14 “GOOD” NIHSS >14 mRS: 0 1 2 3 4 5 6 All NIHSS “GOOD” NNT = 9 NNT = 3

81. Stroke 2006 Summary The NIHSS helps quantify and stratify acute stroke The NIHSS helps quantify and stratify acute stroke Key aspects of the stroke-focused (NIH scale) neuro exam: LOC, vision, motor, coordination, sensation, language Key aspects of the stroke-focused (NIH scale) neuro exam: LOC, vision, motor, coordination, sensation, language Understanding the mRS, BI, and GOS can aid interpretation of outcome in stroke clinical trials. Understanding the mRS, BI, and GOS can aid interpretation of outcome in stroke clinical trials.

82. Stroke 2006 Question: Use of IV tPA This patient’s stroke is deemed to be moderate to severe in its severity and is a suitable candidate for thrombolytic therapy with IV tPA. Which of the following is your viewpoint regarding the use of IV tPA given the published efficacy data?This patient’s stroke is deemed to be moderate to severe in its severity and is a suitable candidate for thrombolytic therapy with IV tPA. Which of the following is your viewpoint regarding the use of IV tPA given the published efficacy data?

83. Stroke 2006 Question: Use of IV tPA A. If IV tPA is indicated, I use it because the clinical data supports its use and I am adequately supported in its use.

84. Stroke 2006 Question: Use of IV tPA B. Although I am not opposed to the use of tPA, I do not use it often because patients rarely meet the criteria for use in the ED.

85. Stroke 2006 Question: Use of IV tPA C. I try not to use tPA because the published efficacy data does not adequately support its use and because I am not well supported to use it.

86. Stroke 2006 Question: Use of IV tPA D. I simply am so concerned about the risk of a symptomatic ICH that I cannot bear to use this drug when treating stroke patients such as this one.

87. Stroke 2006 Question: Use of IV tPA E. I leave the tPA use decision to the stroke team or neurology consultant.

88. Stroke 2006 Question: Use of IV tPA F. Haven’t we discussed tPA enough already?

89. Stroke 2006 Question: Use of IV tPA A. A.Clinical data supports its use B.Patients rarely meet the criteria C.Published efficacy data does not adequately support its use D.Concerned about the risk of a symptomatic ICH E.Decided by the stroke team F.Haven’t we discussed tPA enough already?

90. Stroke 2006 Question: tPA Data Regarding the reanalysis of the NINDS tPA clinical trial data and the phase IV tPA use data, which of the following describe your understanding of the info?Regarding the reanalysis of the NINDS tPA clinical trial data and the phase IV tPA use data, which of the following describe your understanding of the info?

91. Stroke 2006 Question: tPA Data A. I understand that the reanalysis of the NINDS data suggests that there is a real treatment effect and that the phase IV data confirms that the outcomes of the NINDS study can be replicated in clinical practice.

92. Stroke 2006 Question: tPA Data B. I know that the NINDS clinical trial data was confirmed, but the numbers are too small to allow for widespread clinical use, even with confirmatory phase IV clinical data.

93. Stroke 2006 Question: tPA Data C. I have trouble believing phase IV reports, since they are inherently biased, making the use of tPA still somewhat experimental in my practice.

94. Stroke 2006 Question: tPA Data D. I do not have enough familiarity with the reanalysis or the phase IV publications, such that I have not changed my tPA clinical practice.

95. Stroke 2006 Question: tPA Data E. Why was the data reanalyzed, and what is a phase IV study?

96. Stroke 2006 Question: tPA Data A. A.I understand the reanalysis of the NINDS data & phase IV data B.Numbers are too small to allow for widespread clinical use. C.I have trouble believing phase IV reports and have not changed D.I do not have enough familiarity E.What is a phase IV study?

97. Stroke 2006 NINDS Trial Results % Patients with Favorable Outcome t-PA Placebo t-PA Placebo No. of patients: 312 157145 Modified Rankin Scale 40%28% Glasgow Outcome Scale 43%32% NIHSS34%20% Symptomatic ICH (within 36 hr) 6.4%0.6% Death (by 90 days) 17%21%

98. Stroke 2006 IV Thrombolysis  14% absolute increase for the best clinical outcomes (mRS of 0-1).  Benefit = Need to treat eight patients with tPA in order to have one additional patient with this best outcome.  6% absolute increase in the number of symptomatic ICH.  Harm = Will have one symptomatic ICH for every 16 patients treated with tPA.  2 patients will have a minimal or no deficit for every patient with a symptomatic ICH

99. Stroke 2006 Meta-analyses

100. Meta-analyses Wardlaw et al. Wardlaw et al. Net benefit despite hazards Net benefit despite hazards For 1000 treated up to 6hrs: For 1000 treated up to 6hrs: 55 improve, 20 die 55 improve, 20 die Heterogeneity, wide CI make results unreliable Heterogeneity, wide CI make results unreliable Additional trial data required Additional trial data required

101. Stroke 2006 Meta-analyses Graham et al., 15 published reports Graham et al., 15 published reports ICH rate 5.2%, total death rate 13.4% ICH rate 5.2%, total death rate 13.4% All better than NINDS All better than NINDS Lysis can be used safely across wide variety of practice settings Lysis can be used safely across wide variety of practice settings

102. Stroke 2006 Meta-analyses Hacke et al. Hacke et al. 6 randomized trials 6 randomized trials Sooner thrombolytics given the greater the benefit Sooner thrombolytics given the greater the benefit Particularly when given within 90 minutes of onset Particularly when given within 90 minutes of onset

103. Stroke 2006 CONTROVERSY: Meta-analysis Hoffman and Cooper Hoffman and Cooper Pooled data can not replace new or confirmatory data Pooled data can not replace new or confirmatory data Meta-analyses did not include streptokinase trials which were negative Meta-analyses did not include streptokinase trials which were negative No reason to exclude streptokinase No reason to exclude streptokinase

104. Stroke 2006 Phase IV tPA trials Author Eligible patients Patients receiving tPA(%) Mean time to Rx Median NIHSS score Favorable outcome % ICH % Symptom atic ICH % Protocol deviation NINDS3121431-54%10.9%6.4% Chiu103530(2.9%)2’37”1463%10%6.6% Tanne189>2’11-159%5.8%30% Wang90057(6.3%)2’28”1544-54%9%5%9% Buchan154068(4.4%)1595%31%9%16% Albers3892’44”1335-43%11.5%3.3%33% Katzan394870(1.8%)1222%15.7%50% Chapman255646(1.8%)2’45”1430-48%9%2.2%17% Grotta1689269(16%)2’17”1433%4.5%13% Bravata631517%6%67% Total12,282928(5.8%)2’25”10-1533-95%9.6%5.2%13-67%

105. Stroke 2006 Re-analysis

106. NINDS Re-analysis Does the protocol work? Does the protocol work? Do subgroup imbalances invalidate the entire trial? Do subgroup imbalances invalidate the entire trial? What about BP? What about BP?

107. Stroke 2006 Baseline NIHSS Imbalance NIHSS Score 0-56-1011-1516-20 > 20 No. of patients Placebo(n=312)1683667077 t-Pa(n=310)4267657363 Chi-square (4 DF) = 14.8; p = 0.005

108. Stroke 2006 OTT Analysis Report Review Committee had concerns about analyzing OTT as a continuous variable Review Committee had concerns about analyzing OTT as a continuous variable Uncertainty about the exact time of stroke onset. Uncertainty about the exact time of stroke onset. OTT distribution was nonlinear with 25% of all the patients having OTT values of either 89 or 90 minutes. OTT distribution was nonlinear with 25% of all the patients having OTT values of either 89 or 90 minutes.

109. Stroke 2006 Symptom onset vs Cumulative % Time from symptom onset to treatment (minutes) Cumulative percentage

110. Stroke 2006 NINDS ICH Analysis # of Risk Factors # of patients treated with t-PA (n=310) # Symptomatic ICHs (# of placebo patients with ICH) Percentage (%) 0114 2 (1) 1.8 1144 7 (1) 4.9 > 1 521121.2 Risk Factors for ICH: Baseline NIHSS > 20 Baseline NIHSS > 20 Age > 70 years Age > 70 years Ischemic changes present on initial CT Ischemic changes present on initial CT Glucose > 300 mg/dl (16.7 mmol/L) Glucose > 300 mg/dl (16.7 mmol/L)

111. Stroke 2006 IV Thrombolysis  The independent reanalysis of the NINDS tPA clinical trial confirms the results from the initial NEJM publication  Support the use of tPA in stroke patients within three hours of symptom onset  Number needed to treat calculation based on this reanalysis confirms that approximately 8-10 patients need to be treated with tPA in order to cause one extra patient to have the best clinical outcome.  2 patients will improve for every one that develops a symp ICH

112. Stroke 2006 EM Physicians and Lysis Brown et al. Brown et al. 1,105 of 2600 ACEP members responded 1,105 of 2600 ACEP members responded 40% not likely to use thrombolytics 40% not likely to use thrombolytics 65% risk of ICH 65% risk of ICH 23% perceived lack of benefit 23% perceived lack of benefit 12% both 12% both Upper limit ICH rate 3.4% Upper limit ICH rate 3.4% Lowest acceptable relative improvement 40% Lowest acceptable relative improvement 40%

113. Stroke 2006 Informed Consent: Documentation With tPA, there is a 30% greater chance of a good outcome at 3 months With tPA, there is a 30% greater chance of a good outcome at 3 months With tPA use, there is 10x greater risk of a symptomatic ICH (severe bleeding stroke) With tPA use, there is 10x greater risk of a symptomatic ICH (severe bleeding stroke) Mortality rates at 3 months are the same regardless of whether tPA is used Mortality rates at 3 months are the same regardless of whether tPA is used 2 patients will have a minimal or no deficit for everyone patient with a symptomatic ICH 2 patients will have a minimal or no deficit for everyone patient with a symptomatic ICH

114. Stroke 2006 Documentation Just as important Just as important “The patient is NOT a candidate for tPA because…” “The patient is NOT a candidate for tPA because…”

115. Stroke 2006 Question: Utilizing Tests Many diagnostic tests are available when attempting to intervene positively in acute stroke patients. If the initial CT is negative for hemorrhage, how do you utilize tests such as MRI, MRA, CTA, or cerebral angiography when treating stroke patients?Many diagnostic tests are available when attempting to intervene positively in acute stroke patients. If the initial CT is negative for hemorrhage, how do you utilize tests such as MRI, MRA, CTA, or cerebral angiography when treating stroke patients?

116. Stroke 2006 Question: Utilizing Tests A. I do not know when these tests are indicated in acute ischemic stroke patients, and so do not order them in the ED.

117. Stroke 2006 Question: Utilizing Tests B. I am aware that these tests may enhance the ability to diagnose the vascular lesion responsible for the stroke, but I rely on my neurology consultants to determine the need for these tests.

118. Stroke 2006 Question: Utilizing Tests C. I know that these tests are most useful when considering advanced stroke therapies such as IA thrombolysis or clot retrieval, and only order them when the patient is due to have an interventional radiology procedure.

119. Stroke 2006 Question: Utilizing Tests D. I order these tests often in order to expedite the diagnostic workup of my ED stroke patients, whether these patients are to receive IV tPA or who might receive an acute interventional radiology procedure.

120. Stroke 2006 Question: Utilizing Tests E. Have any of these diagnostic tests been proven to be effective at improving outcome in stroke patients?

121. Stroke 2006 Question: Utilizing Tests A.. A.I do not order them in the ED. B.I rely on my neurology consultants. C.I order them when the patient is due to have an interventional radiology procedure. D.I order these tests often. E.Have these tests been proven to be effective?

122. Stroke 2006 Question: Advanced Therapies There are many options that exist after the three-hour IV tPA window, including IA thrombolysis, the Merci clot retrieval device, and devices that enhance cerebral blood flow. What is your clinical practice regarding these advanced stroke therapies?There are many options that exist after the three-hour IV tPA window, including IA thrombolysis, the Merci clot retrieval device, and devices that enhance cerebral blood flow. What is your clinical practice regarding these advanced stroke therapies?

123. Stroke 2006 Question: Advanced Therapies A. I do not have a clear understanding of these advanced therapies, and do not access them for my stroke patients.

124. Stroke 2006 Question: Advanced Therapies B. I know of these therapies, but my understanding is that they are experimental in nature and are not a part of the standard of care.

125. Stroke 2006 Question: Advanced Therapies C. I have noted these therapies to be used by my neurology consultants on occasion, but I am not sure of the indications for their use.

126. Stroke 2006 Question: Advanced Therapies D. I understand the utility of these interventions, and I aggressively pursue them for my stroke patients who do not meet the IV tPA criteria.

127. Stroke 2006 Question: Advanced Therapies E. Have any of these therapies been proven to be effective in any published clinical trials?

128. Stroke 2006 Question: Advanced Therapies A. A.Do not access them. B.Experimental in nature. C.used by my neurology consultants on occasion. D.I aggressively pursue them. E.Have any of these therapies been proven to be effective in any published clinical trials?

129. Foundation for Education and Research in Neurological Emergencies Stroke Care 2006: Clinical Consensus and Opportunities June 16, 2006 Treatment of Stroke Beyond Three Hours Thomas G. Brott, MD, Professor of Neurology Mayo Clinic Jacksonville College of Medicine

130. Results I 2776 patients Over 300 hospitals 18 countries Median age 68 years Median baseline NIHSSS 12

131. Results II Median onset-to-treatment time 4 hours Of the 929 (33%) treated within 3 hours, one-third were from studies other than NINDS

132. Results IV Odds Ratios for Favorable Outcome TimeOdds Ratio95% Conf. Interval 0-902.81.8, 4.5 91-1801.51.1, 2.1 181-2701.41.1, 1.9 271-3601.20.9, 1.5

133. What about IA thrombolysis?

136. PROACT II Stroke within 6 hours 2/3 treated with pro-UK (121) 1/3 treated with placebo (59)

137. Results of ProACT II 40% of the UK patients had a good recovery 25% of the control patients had a good recovery P=.04 Absolute % difference=15%...=NNT of ~ 7 FDA did not approve

138. A score of  2 (yellow) on the modified Rankin scale (mRS) indicates a favorable outcome of slight or no disability. A score of 6 represents death. R-proUK = recombinant prourokinase

139. Beyond Thrombolysis: Combination Therapy, Devices, and Other Approaches

141. Concentric Retriever Device With Nitinol Coil (White Arrow) and Inflated Balloon (Black Arrow) Leary MC, et al. Ann Emerg Med. 2003 Jun;41(6):838-46

142. MERCI Recanalization and Outcomes ICA (n=47) MCA (n=80) BL NIHSS1920 TIMI II/III*53%45% NIHSS 10 pts.**33%29% Sx ICH15% 4% Death**51%39% * About half were TIMI III ** At 90 days

143. ICH in 11 (8%) of patients

144. Stroke 2006 Question: Clinical Guidelines Regarding ischemic stroke patients, what is your understanding and use of clinical guidelines?Regarding ischemic stroke patients, what is your understanding and use of clinical guidelines?

145. Stroke 2006 Question: Clinical Guidelines A. I am not aware of any clinical guidelines that direct my care of ischemic stroke patients.

146. Stroke 2006 Question: Clinical Guidelines B. I am sure that there are guidelines that exist from organizations such as the American Stroke Association, but I do not use them because primarily my neurology consultants utilize these guidelines.

147. Stroke 2006 Question: Clinical Guidelines C. I am familiar with guidelines that direct stroke patient care, and I refer to them on occasion in order to optimize my acute care.

148. Stroke 2006 Question: Clinical Guidelines D. I follow clinical guidelines and protocols in my ED because our hospital has integrated them into clinical policies for the institution.

149. Stroke 2006 Question: Clinical Guidelines E. I wish that there were guidelines that would direct my treatment of stroke complications such as elevated blood pressure.

150. Stroke 2006 Question: Clinical Guidelines A. A.Not aware of any clinical guidelines. B.My neurology consultants utilize these guidelines. C.I refer to them on occasion. D.Our hospital has integrated them. E.I wish that there were guidelines.

151. Stroke 2006 Question: Optimal Therapies Regarding neuroprotection in acute ischemic stroke patients, what is your understanding of current optimal therapies?Regarding neuroprotection in acute ischemic stroke patients, what is your understanding of current optimal therapies?

152. Stroke 2006 Question: Optimal Therapies A. I am not aware of any specific neuroprotection therapies for ischemic stroke patients.

153. Stroke 2006 Question: Optimal Therapies B. I believe that the only useful therapies involve ASA use and blood pressure and glucose management in the majority of ischemic stroke patients.

154. Stroke 2006 Question: Optimal Therapies C. Besides BP and glucose control, I consider optimal cerebral blood flow to be another critical neuroprotectant, and I pursue aggressive thrombolysis and clot retrieval of the target vessel in order to achieve it.

155. Stroke 2006 Question: Optimal Therapies D. I am aware of the trials of specific neuroprotectants, and I utilize them in my clinical practice.

156. Stroke 2006 Question: Optimal Therapies E. I do not believe that neuroprotection is possible. Once the initial damage is done, there is no way to protect the infarct zone or ischemic penumbra.

157. Stroke 2006 Question: Optimal Therapies A. A.Not aware of any therapies. B.Only useful therapies involve ASA use and blood pressure and glucose management. C.Optimal cerebral blood flow is another critical neuroprotectant. D.I utilize them. E.I do not believe that neuroprotection is possible.

158. Stroke 2006 Question: Stroke and ICH Consider if this patient had been on warfarin and had an intracerebral hemorrhage of the left temporal lobe of 3 cm diameter associated with moderate edema and mass effect. What might be your management of this ICH patient?Consider if this patient had been on warfarin and had an intracerebral hemorrhage of the left temporal lobe of 3 cm diameter associated with moderate edema and mass effect. What might be your management of this ICH patient?

159. Stroke 2006 Question: Stroke and ICH A. A.I would admit this patient to neurosurgery for further orders.

160. Stroke 2006 Question: Stroke and ICH B. I would transfer this patient to another hospital because I don’t have neurosurgery coverage and/or it is our institution’s protocol.

161. Stroke 2006 Question: Stroke and ICH C. I would be able to manage BP, ICP, the airway, and ICH complications in the ED prior to disposition to another service for admission.

162. Stroke 2006 Question: Stroke and ICH D. Not only would I manage the patient as in (C.) above, I would also discuss the use of Factor VIIa with neurosurgery in this ICH patient’s care.

163. Stroke 2006 Question: Stroke and ICH D. I am aware of ICH management guidelines, including those that govern the care of patients with an elevated INR, and would follow these guidelines in managing this patient.

164. Stroke 2006 Question: Stroke and ICH A. Admit to neurosurgery. B. Transfer for neurosurgery care. C. I can manage pt prior to transfer. D. FVIIa is an issue I would address. E. I know how to manage elevated INRs in pts who are on warfarin.

165. Stroke 2006 70 yo man with HTN and DM on aspirin has a small left parietal hemorrhagic stroke. Which of the following do you recommend? a) Supportive care only b) DDAVP c) PCC d) rFactor VII

166. Stroke 2006 70 yo man with HTN and DM on coumadin has a small left parietal hemorrhagic stroke. Which of the following do you recommend? a) Supportive care only b) DDAVP c) PCC and Vit K d) rFactor VII and Vit K e) FFP and Vit K

167. Stroke 2006 70 yo man with HTN and DM receives r-tPA: during the infusion his mental status declines and repeat CT shows a hemorrhagic stroke. Which of the following do you recommend? a) FFP b) cryoprecipitate c) PCC and Vit K d) rFactor VII and Vit K

168. Stroke 2006 Conclusions Important EM patient clinical area Important EM patient clinical area Many questions Many questions Some areas of consensus Some areas of consensus Many areas of opportunity Many areas of opportunity Further work is needed Further work is needed The interest is there The interest is there

169. Stroke 2006 Questions? Thank you! ferne@ferne.org edsloan@uic.edu www.ferne.org ferne_nyacep_2006_stroke_finalcd 9/7/2015 6:17 AM