1. Journal Club: The ED Management of Intracerebral Hemorrhage Patients Journal Club: The ED Management of Intracerebral Hemorrhage Patients Nils G. Wahlgren, MD, PhD

2. Nils G. Wahlgren, MD, PhD Associate Professor Clinical Neuroscience Karolinska Institutet Stockholm, Sweden Nils G. Wahlgren, MD, PhD

3. Head of Clinical Stroke Programme and Stroke Research Unit Department of Neurology Karolinska University Hospital Stockholm, Sweden Nils G. Wahlgren, MD, PhD

4. Objectives for this presentation Present a professional reaction to recent publications on management of haemorrhagic stroke Present a method for broad implementation of acute stroke treatments

5. Nils G. Wahlgren, MD, PhD

9. 1. Suspected victims of hemorrhagic stroke should be transported without delay to the nearest hospital providing acute stroke care. Neurointensive care, neuroradiology and neurosurgery services should be available in such hospital (grade C).

10. Nils G. Wahlgren, MD, PhD 2. CT scan of the head is the most important diagnostic procedure in the initial evaluation of patients with suspected ICH (grade C). MRI is as accurate as CT examination for the detection of acute ICH (grade A), and it may be better for the detection of chronic ICH.

11. Nils G. Wahlgren, MD, PhD 5. Specific treatment of ICH is still controversial. As yet, an advantage of neurosurgical intervention over medical treatment has not been established. In the past, there has not been any RCT on medical treatment for spontaneous ICH. Recently, three RCTs evaluating new strategies for the treatment of the ICH have been completed.

12. Nils G. Wahlgren, MD, PhD 5. Three ICH RCTs: a. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial ICH (The International STICH trial); b. Stereotactic aspiration combined with instillation of fibrynolitic agent (The SICHPA trial); c. Ultra-early haemostatic therapy by using the recombinant activated factor VIIa (The Novo-7 trial)

13. Nils G. Wahlgren, MD, PhD 5.1. Main results of STICH trial There is no evidence of an overall benefit of early surgery when compared to initial conservative treatment. One finding in a predefined subgroup, that patients with superficial hematomas might benefit from surgery (craniotomy), needs further exploration.

14. Nils G. Wahlgren, MD, PhD 5.2. The result of SICHPA trial The trial was prematurely stopped because of low recruitment. A cautious conclusion could be made that stereotactic aspiration of supratentorial hematoma after instillation of a plasminogen activator can be performed safely. It may reduce the hematoma volume significantly.

15. Nils G. Wahlgren, MD, PhD 5.3. Main results of Novo-7 trial This was a phase IIb trial which included 400 patients with acute ICH. Treatment with rFVIIa within 4 hours reduced hematoma expansion, decreased mortality, and improved clinical outcome significantly, despite slight increase in the risk of thromboembolic events. A phase III trial is needed to confirm the beneficial effect of rFVIIa in acute ICH.

16. Nils G. Wahlgren, MD, PhD 6. Further statements regarding surgical evacuation (all grade C): a. In cerebellar hemorrhage > 3cm in diameter with hydrocephalus, neurological deterioration or brainstem compression, surgical evacuation should be performed urgently.

17. Nils G. Wahlgren, MD, PhD 6. Further statements regarding surgical evacuation (all grade C): b. Intraventricular ICH plus hydrocephalus should be treated with ventricular drainage. c. In supratentorial hemorrhages consider removal of clots if there is deterioration from GCS 9–12, or if ICP rises by craniotomy if superficial (within 1 cm of cortical surface) by aspiration if deep (need more trials)

18. Nils G. Wahlgren, MD, PhD European dilemma: 1,000,000 strokes/year 500,000 ’independent’ after 12 months 200,000 die < 12 months 300,000 ’dependent’ after 1 year 55 billion Euro

19. Nils G. Wahlgren, MD, PhD Strategies to reduce acute lesion Stroke Units Thrombolysis Hemostasis Hemicraniectomy

20. Nils G. Wahlgren, MD, PhD Several interventions are proven efficacious, but: What good is that the results from Randomised Controlled Trials are forgotten in the Archives? Stroke Units UNDERUSED Thrombolysis Anticoagulation in AF Carotid surgery UNDERUSED

21. Nils G. Wahlgren, MD, PhD The appropriateness of randomised controlled trials or quality monitoring registers depend on level of evidence for a treatment Evidence for effect and safety of treatment Unclear Clear Inherent risks with treatment, e.g. bleedings Potential for continuous improvement Treatment new to many None of above Randomised controlled trials Safety/ quality monitoring No monitoring needed

22. Nils G. Wahlgren, MD, PhD Maps courtesy of www.theodora.com/maps used with permissionwww.theodora.com/maps 324 active centres in 24 countries plus >60 centres, 2 countries pending 5442 patients (June 29, 2005) Scientific Committee Brain Imaging Committee National Committees National & Local Coordinators >1000 users of the SITS database Safe Implementation of Thrombolysis in Stroke (SITS) International network of medical professionals dedicated to safe implementation of thrombolysis using the International Stroke Thrombolysis Register (SITS-ISTR) as a tool Conducts a safety monitoring study (SITS- MOST) to ensure safe broad implementation and permanent licence in European Union SITS is an academic initiative to support implementation of stroke treatment – so far within thrombolysis but big overlap with haemorrhage management

23. Nils G. Wahlgren, MD, PhD Maps courtesy of www.theodora.com/maps used with permissionwww.theodora.com/maps SITS is an academic initiative to support implementation of stroke treatment – thrombolysis and haemostasis Baseline + results data for rt-PA treated patients Immediate statistical report Centre Country Total Feedback Improved effect Improved safety

24. Nils G. Wahlgren, MD, PhD Recruitment in SITS is now (Aug 05) >6000 patients in 324 active centers – great potential for rapid treatment implementation Patients recruitedCenters recruited 2003 2004 2005

25. Nils G. Wahlgren, MD, PhD SITS International Broad implementation Amplification The purpose of SITS is two-dimensional

26. Nils G. Wahlgren, MD, PhD The proportion of SITS-MOST centres with no previous experience of thrombolysis is growing Number of centers 1.Experienced center: Participated in ECASS I/II or treated at least 5 patients before joining SITS. New Center: No such experience 17% 37% 51% 100%=6 100%=139 100%=311 Experienced centers 1 New centers 1 Jan 2003Dec 2003Dec 2004 SITS-MOST reaches non-expert centers that might not otherwise dare to start “Without the support and scientific approach from SITS we would not have dared to start thrombolysis treatment here”

27. Nils G. Wahlgren, MD, PhD Conclusions Karolinska Stroke Update: NovoSeven is very promising for treatment of haemorrhagic stroke SITS International – professional network is an effective instrument for broad imlementation of management of haemorrhagic stroke

28. Nils G. Wahlgren, MD, PhD

29. Questions?? www.strokeupdate.org www.acutestroke.org Nils Wahlgren, MD, PhD Questions?? www.strokeupdate.org www.acutestroke.org Nils Wahlgren, MD, PhD nils.wahlgren@karolinska.se www.strokeupdate.org ferne_aaem_france_2005_wahlgren_ich_jclub.ppt 5/10/2015 4:58 AM Nils Wahlgren, MD, PhD