1. William Dalsey, MD, FACEP Hemorrhagic Stroke Patient Management in the ED: What are the Current Roles of Operative Intervention and Factor VIIa?

2. William Dalsey, MD, FACEP 2006 Advanced Emergency & Acute Care Medicine and Technology Conference 2006 Advanced Emergency & Acute Care Medicine and Technology Conference

3. William Dalsey, MD, FACEP Emergency Medicine Associates Atlantic City, NJ September 26-27, 2006

4. William Dalsey, MD, FACEP William Dalsey, MD, FACEP Chairman Department of Emergency Medicine Kimball Medical Center Lakewood, NJ

5. William Dalsey, MD, FACEP Disclosures All past advisory board or speakers’ bureau activities have expired within the past year All past advisory board or speakers’ bureau activities have expired within the past year

6. William Dalsey, MD, FACEP Case Presentation

7. William Dalsey, MD, FACEP Case Presentation 52 year old male 52 year old male Right sided weakness one hour Right sided weakness one hour Gradual onset and progressive Gradual onset and progressive PMH: Hypertention, Smoker PMH: Hypertention, Smoker VS: HR 90 RR 14 BP 195/110 VS: HR 90 RR 14 BP 195/110

8. William Dalsey, MD, FACEP Case Presentation… Slow to respond verbally but appropriate Right sided weakness Able to protect his airway BGM 120mg/dl No evidence of trauma or toxidrome What do you do now?

9. William Dalsey, MD, FACEP Pathophysiology of ICH Regarding Hemorrhage Growth ? Pathophysiology of ICH Regarding Hemorrhage Growth ? Intra-arterial bleeding into parenchyma 78-88% from chronic hypertention Secondary ICH: amyloid, coumadin, aneurysms, AVMs, tumors, drug use, thrombolytics ….. 23-58% mortality at six months Half of deaths occur within 48 hs Only 20% living independently at 6 months

10. William Dalsey, MD, FACEP Risk Factors ICH Hypertension Cerebral amyloid angiopathy Alcohol Hypocholesterolemia Aspirin Heparin, coumadin, thrombolytics Vascular abnormalities Drug abuse Trauma Intracranial surgery Vasculitis

11. William Dalsey, MD, FACEP Pathophysiology Primary Injury Primary Injury Secondary Injury: Toxic effect, proteins, edema, elevation ICP, obstructive hydrocephalus Secondary Injury: Toxic effect, proteins, edema, elevation ICP, obstructive hydrocephalus

12. William Dalsey, MD, FACEP Prognosis/Initial Management Posterior Fossa vs Lobar GCS scores Size of Hemorrhage Early Ventricular Blood Supportive Management: airway, hypoxia, glucose, MAP, seizures the astonis hing results Compare the results with a conventional training protocol. Most people do at least two exercises per muscle group, perform three sets and perhaps 12 or 15 reps per set. Allowing just five seconds per rep, that makes for at least 36 minutes of exercise per workout. This is usually done three times per week. So in six weeks, a conventional program would involve 648 minutes of exercise. That's 42 times more than the subjects in our study. Are your results in the last six weeks 42 times better than theirs? I doubt it. perform ance improve ment Remember, these golfers were exercising in a way that did not involve stretching or moving the weight over a full range of motion. So how did this affect a full range of motion activity like a golf drive? Every one of them showed an improvement. The increase in drive distance varied from 5 to 31 yards. Keep in mind that these subjects had been golfing for up to 40 years and had handicaps as low as eleven. So getting any improvement in golfers who already play at this level is impressive. Getting it with 14 minutes of exercise spread over six weeks is truly revolutionary. The fact is every sport -- even a finesse sport like golf -- is improved by an increase in strength. Muscles are responsible for all movement in the body and stronger muscles deliver more power to every aspect of movement, irrespective of its range of motion.increase in strength Since this study, I've gone on to improve this method of training. Further research showed that static hold times could be reduced to even less than what the golfers used. Workouts can be spaced further apart as a trainee gets stronger. I work with advanced trainees who train once every six weeks, yet they gain strength on every exercise each time they work out. The weights they hoist are enormous. I believe the time is coming when most people will have a better understanding of the role of proper, efficient strength training methods and frequency. For the guy who wants maximum results with minimum time invested, an ultra-brief but ultra-intense workout will be performed about as often as he gets a haircut. Anything more is just lifting weights as a busy work hobby. Train smart!

13. William Dalsey, MD, FACEP Intracerebral Hemorrhage How does hemorrhage growth relate to clinical status and the ICH patient ?

14. William Dalsey, MD, FACEP Intracerebral Hemorrhage Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. 1993 Stroke http://stroke.ahajournals.org/cgi/content/abstract/24/7/987

15. William Dalsey, MD, FACEP Intracerebral Hemorrhage Retrospective study of 188 ICH patients Hemorrhage volume and GCS scores ICH bleeding volumes >60 cm 3 and GCS < 9 mortality 91% ICH volumes 8 mortality 19%

16. William Dalsey, MD, FACEP Intracerebral Hemorrhage The ABC’s of Measuring Intracerebral Hemorrhage Kothari RU, Brott TG, Broderick JP et. al. Stroke 1996:27:1304-5

17. William Dalsey, MD, FACEP Intracerebral Hemorrhage ½ the product of the diameter of the largest bleed times the perpendicular measurement times the number of slices times the diameter of the slices

18. William Dalsey, MD, FACEP Intracerebral Hemorrhage Early hemorrhage growth in patients with intracerebral hemorrhage. Brott T, Broderick J, Kothari R, Barsan W, Tomsick T, Sauerbeck L, Spilker J, Duldner J, Khoury J. Early hemorrhage growth in patients with intracerebral hemorrhage. Brott T, Broderick J, Kothari R, Barsan W, Tomsick T, Sauerbeck L, Spilker J, Duldner J, Khoury J. 1997 Stroke 1997 Stroke http://stroke.ahajournals.org/cgi/content/full/28/1/1 http://stroke.ahajournals.org/cgi/content/full/28/1/1 http://stroke.ahajournals.org/cgi/content/full/28/1/1

19. William Dalsey, MD, FACEP Intracerebral Hemorrhage Prospective observational study Prospective observational study CT at time zero, I hour and 20 hours CT at time zero, I hour and 20 hours In 103 patients In 103 patients In a total of 103 patients with these scans, 26% had a growth in volume > 33% by 1 hour, and 38 % had a similar growth by 20 hours In a total of 103 patients with these scans, 26% had a growth in volume > 33% by 1 hour, and 38 % had a similar growth by 20 hours These patients had a greater decrease in NIHSS and a greater likelihood that there would be a > 2 drop in GCS. These patients had a greater decrease in NIHSS and a greater likelihood that there would be a > 2 drop in GCS.

20. William Dalsey, MD, FACEP Surgery in ICH ? What were the recommendations for Surgical Therapy of ICH established by the AHA Stroke Council in 1999? < 10cm3, large bleeds and GCS <4 Cerebellar, <45 yo, structural lesions, large lobar bleeds

21. William Dalsey, MD, FACEP Intracerebral Hemorrhage Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomized trial. Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, Karimi A, Shaw MD, Barer DH; STICH investigators. 2005 Lancet http://www.thelancet.com/journal/vol365/iss9457/abs/llan. 365.9457.analysis_and_interpretation.32126.1

22. William Dalsey, MD, FACEP STICH TRIAL Prospective randomized trial 1033 patients Prospective randomized trial 1033 patients Surgery w/in 24 hs vs. medical management Surgery w/in 24 hs vs. medical management Outcome at 6 months Outcome at 6 months Results:23.8% favorable outcomes in the “Initial Conservative Treatment” group compared with 26.1% in the “Early Surgical Group.” These differences were not significant (odds ratio 0.89; 95% CI, 0.66- 1.10). There was no difference in mortality of 36.3% with 37.4%. Results:23.8% favorable outcomes in the “Initial Conservative Treatment” group compared with 26.1% in the “Early Surgical Group.” These differences were not significant (odds ratio 0.89; 95% CI, 0.66- 1.10). There was no difference in mortality of 36.3% with 37.4%.

23. William Dalsey, MD, FACEP STICH Limitations Physician choice in terms of the specific procedure Patients were randomized only when uncertain if surgical or medical treatment was best In 12% of patients assigned to surgery either the surgery did not occur or it was delayed for more than 24 hours In patients assigned to medical treatment 26% crossed-over to surgery.

24. William Dalsey, MD, FACEP ICH and Surgery 2005 Priorities for Clinical Research in Intracerebral Hemorrhage. Report From a National Institute of Neurological Disorders and Stroke Workshop. 2005 Stroke;36:e23 Priorities for Clinical Research in Intracerebral Hemorrhage. Report From a National Institute of Neurological Disorders and Stroke Workshop. 2005 Stroke;36:e23 No clear benefit No clear benefit Cerebellar Hemorrhage Cerebellar Hemorrhage Life-threatening Lobar Hemorrhage Life-threatening Lobar Hemorrhage Future Studies Future Studies

25. William Dalsey, MD, FACEP ICH and Factor VIIa What is the role for Factor VIIa in the management of ICH patients?

26. William Dalsey, MD, FACEP ICH and Factor VIIa Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage. Mayer SA, Brun NC, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T; Europe/AustralAsia NovoSeven ICH Trial Investigators. 2005 Stroke http://stroke.ahajournals.org/cgi/content/abstract/36/1/74

27. William Dalsey, MD, FACEP ICH and Factor VIIa Recombinant activated factor VII for acute intracerebral hemorrhage. Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T; Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators. 2005 NEJM http://content.nejm.org/cgi/content/short/352/8/777

28. William Dalsey, MD, FACEP ICH and Factor VIIa P rospective, randomized study of 399 patients Three doses of recombinant factor VIIa dosed within one hour of the baseline CT Growth of ICH and outcomes at 90 days

29. William Dalsey, MD, FACEP ICH and Factor VIIa Results: Improved Outcomes 29% vs 16% ICH Growth 69% vs 54% Severe Disability 28% vs 18% Mortality Complications: CVA, AMI 7% vs 2%

30. William Dalsey, MD, FACEP ICH and Factor VIIa What is the role for Factor VIIa in the management of ICH patients who have an elevated INR due to warfarin use?

31. William Dalsey, MD, FACEP ICH and Factor VIIa Recombinant factor VIIa for rapid reversal of warfarin anticoagulation in acute intracranial hemorrhage. Freeman WD, Brott TG, Barrett KM, Castillo PR, Deen HG Jr, Czervionke LF, Meschia JF. 2004 Mayo Clinic Proc http://www.mayoclinicproceedings.com/Abstra ct.asp?AID=775&Abst=Abstract&UID

32. William Dalsey, MD, FACEP Conclusions Re: Factor VIIa Priorities for Clinical Research in Intracerebral Hemorrhage. Report From a National Institute of Neurological Disorders and Stroke Workshop. Priorities for Clinical Research in Intracerebral Hemorrhage. Report From a National Institute of Neurological Disorders and Stroke Workshop. 2005 Stroke 2005 Stroke http://stroke.ahajournals.org/cgi/conten t/abstract/36/3/e23 http://stroke.ahajournals.org/cgi/conten t/abstract/36/3/e23 http://stroke.ahajournals.org/cgi/conten t/abstract/36/3/e23 http://stroke.ahajournals.org/cgi/conten t/abstract/36/3/e23

33. William Dalsey, MD, FACEP Future Research Priorities for Clinical Research in Intracerebral Hemorrhage. Report From a National Institute of Neurological Disorders and Stroke Workshop. 2005 Stroke;36:e23 Priorities for Clinical Research in Intracerebral Hemorrhage. Report From a National Institute of Neurological Disorders and Stroke Workshop. 2005 Stroke;36:e23

34. William Dalsey, MD, FACEP Guidelines for ICH Care? Guidelines for the management of spontaneous intracerebral hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Broderick JP, Adams HP Jr, Barsan W, Feinberg W, Feldmann E, Grotta J, Kase C, Krieger D, Mayberg M, Tilley B, Zabramski JM, Zuccarello M. Guidelines for the management of spontaneous intracerebral hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Broderick JP, Adams HP Jr, Barsan W, Feinberg W, Feldmann E, Grotta J, Kase C, Krieger D, Mayberg M, Tilley B, Zabramski JM, Zuccarello M. 1999 Stroke 1999 Stroke

35. William Dalsey, MD, FACEP Intracerebral Hemorrhage So, what happened to my patient? So, what happened to my patient?

36. William Dalsey, MD, FACEP Questions? www.FERNE.org sparkledmd@aol.com ferne_ema_2006_dalsey_ich_092606_final.cd 5/3/2015 4:54 PM