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Ten Things to Know in Intracerebral Hemorrhage

Ten Things to Know in Intracerebral Hemorrhage. Edward C. Jauch, MD, MS. Assistant Professor Director of Research Department of Emergency Medicine University of Cincinnati College of Medicine Faculty, Greater Cincinnati / Northern Kentucky Stroke Team. Disclosure. Novo Nordisk

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Ten Things to Know in Intracerebral Hemorrhage

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  1. Ten Things to Know in Intracerebral Hemorrhage

  2. Edward C. Jauch, MD, MS Assistant ProfessorDirector of ResearchDepartment of Emergency MedicineUniversity of Cincinnati College of MedicineFaculty, Greater Cincinnati / Northern Kentucky Stroke Team

  3. Disclosure • Novo Nordisk • Consultant & Site investigator phase III trial • American Heart Association • ASA and ACLS Stroke Guidelines Committee • Various AHA Committees • NINDS ventricular and ICH aspiration trials • Genentech providing drug

  4. Point 1 Intracerebral Hemorrhage is Bad!

  5. Ethnicity of ICH Risk • Age and sex adjusted rate • U.S. 15 per 100,000 • World wide 10-20 per 100,000 • Rates: 13.5 per 100,000 Caucasian38 per 100,000 African Americans 55 per 100,000 Japanese

  6. Mortality and Morbidity • Outcome: • 35-52% dead at 1 month • 50% of deaths within 48o • 10% independent at 30 days • 20% independent at 6 mos • Lifetime ICH cost $125K # patients Modified Oxford Handicap Scale (Broderick, Stroke 1993;24:987- 93)

  7. Point 2 Intracerebral Hemorrhage is Like Acute Ischemic Stroke Sort of

  8. Similar Pathophysiology

  9. Primary Risk Factors • Vascular malformations • Moyamoya / aneurysms • Infections • Vasculitis • Mycotic aneurysms • Cerebral venous thrombosis • Genetic • Apolipoprotein E ε4 • Age • Hypertension • Alcohol intake • Gender (M > F) • Race • Smoking • Diabetes

  10. Location • Lobar • Associated with amyloid angiopathy • Nonlobar • Due to hypertension • Cerebellar • Brain stem Cortex Thalamus Basal ganglia Pons Cerebellum

  11. Point 3 ICH is Dynamic

  12. ICH Progression • Symptoms often progress, associated with ICH growth • 2/3 with progression of symptoms • 1/3 maximal at onset • Within 3 hours from onset: • 26% with >33% growth in next 1o • 12% with >33% growth 1-20o (Brott, Stroke 1997;28:1-5)

  13. Point 4 Size Matters

  14. 28 mL 43 mL (Image courtesy T. Brott, MD)

  15. Prognosis • Worse • Volume > 60 cm3 and GCS < 9 • 91% dead at 30 days • Patients with > 30 cm3 • 1 / 71 independent at 30 days • Other: age, seizures, intraventricular extension • Better • Volume < 30 cm3 and GCS 9 or higher • 19% dead at 30 days (Broderick, Stroke 1993;24:987- 93)

  16. Hematoma Volume • Formula for volume of an ellipsoid • 4/3π (A/2)(B/2)(C/2) • Simplified A*B*C / 2 C B A (Kothari, Stroke 1996;27:1304-5)

  17. Point 5 Medical Management The Basics are Important

  18. Current Recommendations for Management of Intracerebral Hemorrhage New guidelines due 2005 (Broderick, Stroke 1999;30(4):905-15) Edward C. Jauch, MD MS FACEP

  19. ICH Management • Immediate stabilization (ABC’s) • Supportive medical care • Frequent comorbidities • Neurologic specific care • Hemorrhage specific interventions

  20. Emergent Evaluation • Baseline labs • CBC, coagulation parameters, electrolytes • Neuroimaging • CT remains gold standard • Identify ICH and complications (hydrocephalus, herniation) • MRI / MRA • For structural abnormalities (AVM, aneurysms) • Angiography • Rarely emergently indicated, identifies vascular issues

  21. Medical Management • ABC’s • Maintain oxygen saturation ≥92% • Rapid sequence intubation • Medical management • Prevention of hyperthermia (<37.5oC) • Glycemic control (<10 nmol/L) • Coagulopathy correction (FFP, vitamin K) • No glycerol, corticosteroids, hemodilution • Secondary complication prevention (EUSI, Cerebrovasc Dis 2003;16:311-318)

  22. Point 6 Medical Management is Important Blood Pressure

  23. Blood Pressure Management • Hypertension very common • MAP > 140 in 34%, > 120 in 78% • Many ‘normalize’ over first 24 hours • General goals • Maintain MAP < 130 mmHg with history of hypertension • Prevent hypotension (SBP < 90 mmHg) • Maintain: • Cerebral perfusion pressure (CPP=MAP-ICP) CPP > 70 mmHg • Central venous pressure from 5-12 mmHg • Optimal blood pressure still to be determined

  24. Blood Pressure Management • Common agents • Labetalol • Nicardipine • Nitroprusside • (theoretical risk of • increasing ICP) • New data suggest SBP < 150 mm Hg (Broderick, Stroke 1999;30(4):905-15) (Ohwaki, Stroke 2004;35:1364-1367)

  25. Point 7 Medical Management is Important Intracranial Pressure

  26. Management of ICP • Definition • ICP > 20 mm Hg for > 5 minutes • Treatment goal • ICP < 20 mm Hg and CPP > 70 mm Hg • Recommendations • ICP monitoring with GCS < 9 • Management • Patient positioning • Osmotherapy • Hyperventilation • Ventricular drainage

  27. Management of ICP • Osmotherapy • Mannitol 0.25-0.5 g/kg every 6 hours up to 5 days • Target mOsm < 310 mmol/L • Hyperventilation • Tidal volume of 12-15 ml/kg • Target pCO2 30-35 mm Hg • Neuromuscular paralysis • Nondepolarizing agents (Broderick, Stroke 1999;30(4):905-15)

  28. Point 8 Medical Management is Important Seizures

  29. Seizures • More common in ICH than you think • Over 25% will seize (vs 6% for ischemic stroke) • Much more common if lobar • Focal with secondary generalization • Most in first 72 hours • Treatment • Phenytoin (minimizes sedation) • Does not convey life-long epilepsy (Vespa, Neurology 2003;60:1441-6)

  30. Point 9 Medical Management is Important Coagulation Correction

  31. Coagulation Correction • Warfarin • FFP 10 ml/kg • Vit K 10 mg IV over 10 mins • Heparin (and some LMWH) • Correct with protamine 10 – 50 mg IVP over 1 – 3 mins • Direct thrombin inhibitors • No antidote, consult hematology • Platelet disorders • Correct with platelets (>100,000) • DDAVP 0.3 µg/kg IV over 30 mins (MGH Stroke Service, 2005)

  32. Point 10 There is Hope on the Horizon

  33. What can be Fixed? • Stop the bleeding • Until now no option? • Remove the blood • Multiple trials without clear impact • Reduce the edema • No treatment yet

  34. Potential Future Tools • Surgery • Surgical patient selection and new approaches • Stereotactic evacuation with tPA • Intraventricular evacuation with fibrinolysis (ITT, DITCH) • Medical therapies • Optimizing blood pressure (ATACH) • Tight glycemic control (THIS) • Neuroprotectives (CHANT, Fast-MAG, hypothermia) • Ultra-early hemostatic therapy (rFVIIa)

  35. Surgical Treatment • Direct evacuation, endoscopic, stereotactic

  36. Surgical Treatment Recommendations • 7000 procedures a year in U.S. despite lack of data • STICH: Largest surgical trial without general benefit (Mendelow, 2005;365:387-97) (Broderick, 1999;30(4):905-15)

  37. Hemostatic Therapy • Few late studies (mostly in SAH*) • Aminocaproic acid • Tranexamic acid* • Ultra-early studies • rFVIIa • Pilot (n=48) • F7ICH-1371 (n=399) • Phase III (n=675) ongoing (Mayer, Stroke 2005;36:74-79) (Mayer, NEJM 2005;352:777-785)

  38. ≤ 60 mins Placebo N = 100 rFVIIa 40 µg/kg N = 100 rFVIIa 80 µg/kg N = 100 rFVIIa 160 µg/kg N = 100 Study Design < 3 hours 24-72 hours 90 days • 2° Efficacy • Mortality • mRS • Barthel Index • E-GOS • NIHSS • GCS • Euro-QOL CT Baseline CT 24 h CT 72 h Patients presenting with stroke-like symptoms 1° Efficacy Percent change in ICH volume at 24 hours Baseline CT scan • Safety • Adverse events until discharge • Serious adverse events until day 90 • Exacerbation of edema 20 Countries 73 Trial Sites (Mayer, NEJM 2005;352:777-785)

  39. % 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 Estimated Mean Percent Change in ICH Volume at 24 Hours Percent Change in ICH Volume by Treatment % 70 52% RR 62% RR 45% RR 65 60 55 50 45 40 35 30 29% * 25 20 16% 14% 14% 15 11% 10 5 0 -5 -10 -15 -20 CombinedTreatment Groups Placebo 40 µg/kg 80 µg/kg 160 µg/kg Treatment Groups *Combined treatment groups vs placebo: P = 0.0112. (Mayer, NEJM 2005;352:777-785)

  40. Modified Rankin Scale at Day 90 0–1 no significant disability 160 µg/kg 2–3 slight to moderate disability 80 µg/kg 4–5 moderately severe to severe disability 40 µg/kg Placebo 0% 20% 40% 60% 80% 100% 6 dead* *29% vs 18% rFVIIa vs placebo, RRR 38%, Chi-square test; P = 0.02 (Mayer, NEJM 2005;352:777-785)

  41. Thromboembolic SAEs Frequency of Thromboembolic SAEs • Arterial thromboembolic SAEs (myocardial ischemia 7 and cerebral infarction 9) with rFVIIa treatment (5%) vs placebo (0%), P = 0.01 • Fatal or disabling thromboembolic SAEs in 2% of rFVIIa-treated patients compared with 2% in the placebo group • Nonsignificant dose trend in events (P = 0.12) (Mayer, NEJM 2005;352:777-785)

  42. Bonus Point Learn from Your Mistakes

  43. Time Will Always Mean Brain! • ICH continue to expand • Early medical management essential • Early coagulation correction critical (drip and ship) • Hemostatic therapy may work best early (Lancet 2004; 363: 768–74)

  44. Same Chain: No Weak Links • Development: Protocol and pathway development • Detection: Early recognition • Dispatch: Early EMS activation • Delivery: Transport & management • Door: ED triage • Data: ED evaluation & management • Decision: Neurologic input, therapy selection • Drug: Thrombolytic (hemostatic) agents • Disposition: Admission or transfer

  45. There May Be Major Barriers • Education • Timely radiology involvement • Access to neurologic expertise • Post treatment management • Availability of ICU beds • Complications occur early • Resources and cost

  46. Key Learning Points • ICH is a dynamic process • Critical management frequently required and required early • General management impacts outcome • Targeted therapies time dependent • Hemostatic therapies may play a role if administered early • Surgery for selected cases

  47. Questions? www.ferne.orgferne@ferne.orgEdward C. Jauch, MD, MSedward.jauch@uc.edu

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