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Current Management of Intracerebral Hemorrhage

Current Management of 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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Current Management of Intracerebral Hemorrhage

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  1. Current Management of 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 Committee • National Institutes of Health • Ventricular and hematoma aspiration trials (Genentech providing drug)

  4. Global Objectives • Review epidemiology of ICH • Discuss current treatment recommendations • Review recent developments in ICH treatment • Discuss lessons from acute ischemic stroke

  5. A Clinical Case

  6. Patient Initial Clinical History • 57 yo male develops sudden onset headache and left sided weakness • Family calls 911 (112, 115, etc) • EMS transport to hospital • Symptoms progress to full hemiplegia • Initial VS: 210 / 120 mmHg, HR 110, R 24

  7. Patient ED Presentation • PMHX: Hypertension for 10 years, hyperlipidemia • SHX: Smoking 30 years • Meds: ACE inhibitor, ASA • ROS: No recent illness or injuries No new medications

  8. Patient ED Presentation • Physical examination: • VS - 220 / 140 mmHg, HR 110, RR 22, T 98.6oF • Neuro (NIHSS = 12) • LOC mildly depressed (GCS 13) • Left facial droop & partial gaze palsy • Dense left hemiplegia • Mild left sensory loss • Speech slurred • Laboratory and ECG normal • Neuroimaging shows

  9. Key Questions • What is your differential diagnosis? • What medical management should be initiated in this patient? • What additional imaging is required? • What laboratory tests should be completed? • What are treatment options and issues?

  10. Lacunar 19% Thromboembolic 6% SAH 13% Cardioembolic 14% Hemorrhagic 26% Ischemic 71% ICH 13% Unknown 32% Other 3% Stroke Subtypes Up to 65,000 ICH per year (Foulkes, NINCDS Stroke Data Bank Stroke, 1988)

  11. ICH Classifications • Primary (80%) • Hypertensive arteriolopathies • Cerebral amyloid angiopathies • Secondary (20%) • Vascular abnormalities • Neoplasms • Coagulation disorders • Anticoagulants or thrombolytic agents • Drugs (cocaine, ephedra, etc) • Trauma

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

  13. Clinical Presentation • Symptoms and signs • 82% change in mental status • >75% hemiparesis/plegia • 63% headache • 22% vomiting • Symptoms • 2/3 with progression of symptoms • 1/3 maximal at onset (Brott, Stroke 1997;28:1-5)

  14. Clinical Presentation by Location • Lobar • Headache (headache location related to ICH site) • Motor, sensory deficit, or VF deficits (not all) • Deep • Unilateral motor, sensory, VF loss • Aphasia (D) or neglect (ND) • Cerebellum • Nausea, vomiting, ataxia, coma • Pontine • Coma, quadriplegia, pinpoint pupils

  15. 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

  16. Pathophysiology • Initial hemorrhage into tissues causes: • Cytotoxic and vasogenic edema formation • Mediators: MMP-9, inflammatory response, blood degradation products • Elevated intracranial pressure due to: • Hematoma mass effect • Perihematomal edema • Intraventricular extension and hydrocephalus • Decreased regional perfusion and herniation

  17. ICH Progression • Symptoms often progress, associated with ICH growth • Within 3 hours from onset: • 26% with 33% or greater growth in next 1 hour • 12% with 33% or greater growth 1-20 hours (Brott, Stroke 1997;28:1-5)

  18. 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)

  19. 28 mL 43 mL (Image courtesy T. Brott, MD)

  20. 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)

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

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

  23. 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

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

  25. 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)

  26. 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

  27. Blood Pressure Management • For now - • 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)

  28. 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

  29. 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)

  30. Seizures • More common in ICH than you think • Over 25% will seizure (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)

  31. 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

  32. Surgical Treatment • Direct evacuation, endoscopic, stereotactic

  33. 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)

  34. 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)

  35. ≤ 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)

  36. % 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)

  37. 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)

  38. 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)

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

  40. What Can We Learn From Acute Ischemic Stroke?

  41. 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)

  42. 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

  43. Door-to-MD: 10 minutes Door-to-”Expert”? 15 minutes Door-to-CT scan: 25 minutes Door-to-Drug: 60 minutes Door-to-Admission 3 hours NINDS RecommendationsSame for ICH? (NINDS Stroke Symposium 2003)

  44. 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

  45. ED Treatment & Patient Outcome • Patient’s GCS declined to 11 over 48o • Mild edema & shift seen on 48o CT • Blood pressure managed with labetalol • Patient required inpatient rehab • Moderately disabled at 3 months but at home

  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. Key Role of Emergency Medicine

  48. Questions?? www.ferne.orgferne@ferne.orgEdward C. Jauch, MD, MSedward.jauch@uc.edu ferne_2005_aaem_france_jauch_ich_fshow.ppt 8/29/2005 1:45 AM

  49. 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

  50. ICH Rate by Age Incidence rate / 100,000 per year

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