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Cerebral Hemorrhage Galen V. Henderson, M.D. Brigham and Women’s Hospital Director, Neuroscience ICU Harvard Medical School.

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Presentation on theme: "Cerebral Hemorrhage Galen V. Henderson, M.D. Brigham and Women’s Hospital Director, Neuroscience ICU Harvard Medical School."— Presentation transcript:

1 Cerebral Hemorrhage Galen V. Henderson, M.D. Brigham and Women’s Hospital Director, Neuroscience ICU Harvard Medical School

2 Disclosures I have no industry relationships

3 Outline Epidemiology Imaging Prognosis Neurogenic stress cardiomyopathy Subclinical seizures Hypertonic saline Protein complex concentrates New treatments

4 Significance of cerebral hemorrhage ICH represents 10 – 15% of all strokes Twice as common as subarachnoid hemorrhage and just as deadly Only 20% live independently at 6 months Worldwide incidence: 10–20 cases per 100,000 population American Heart Association. Heart Disease and Stroke Statistics–2005 Update; Qureshi AI et al. N Engl J Med. 2001;344: Broderick JP et al. Stroke. 1999;30: ; Broderick JP et al. N Engl J Med. 1992;326: Broderick JP, et al. Stroke. 2007;38:1-23.

5 Significance of cerebral hemorrhage 30 day mortality rate 35-52%, half of deaths occur in the first 2 days Mortality rate unchanged over the last 20 years To date no therapies have shown benefit in randomized clinical trials –Surgical evacuation –Osmotic diuretics –Glucocorticoids

6 Intracerebral hemorrhage Subtypes Primary –Hematomas –Microbleeds Secondary –Tumors –Vascular malformation –Aneurysms –Coagulopathy –Trauma –Ischemic stroke with trans. –Drug use Subarachnoid –Aneurysmal –Non-aneurysmal Subdural hematoma Epidural hematoma

7 Qureshi AI et al. N Engl J Med. 2001;344: Broderick JP, et al. Stroke. 2007;38:1-23. Most Common Sites of ICH Pons Cerebral lobes Basal ganglia Thalamus Cerebellum 50% deep 35% lobar 10% cerebellum 6% brainstem

8 Early Hemorrhage Growth in Patients with ICH NIHSS, National Institutes of Health Stroke Scale. Brott T et al. Stroke. 1997;28:1-5. Image courtesy T. Brott, MD.

9 Early Hemorrhage Growth in Patients with ICH 103 patients scanned < 3 hours of onset 38% experienced significant hematoma growth (> 33% increase in volume) –26% within 1 hour of baseline scan –12% between 1- and 20-hour scan ICH growth was associated with clinical deterioration on NIHSS In patients with putaminal ICH, hematoma growth (> 33%) occurs early (shown) NIHSS, National Institutes of Health Stroke Scale. Brott T et al. Stroke. 1997;28:1-5.

10 ICH Volume Powerful Determinant of 30-day Outcome Condition at 30 days (Oxford Handicap Scale) Broderick JP et al. Stroke. 1993;24: Good recovery with volume > 30 mL does not occur

11 28 mL 43 mL Image courtesy T. Brott, MD. Slide No. 12

12 Goldstein, J. N. et al. Neurology 2007;68: Contrast within the hematoma

13 GRE Sequences and Cerebral Amyloid Angiopathy Lobar Hemorrhage Microbleeds

14 The ICH Score Components GCS score 3–42 5–121 13–150 ICH volume, cm 3 >301 <300 IVH Yes1 No0 Infratentorial origin of ICH Yes1 No0 Age, y 801 <800 Total ICH Score0–6

15 Hemphill, J. C. et al. Stroke 2001;32: The ICH Score and 30-day mortality

16 Rost, N. S. et al. Stroke 2008;39: FUNC score prediction tool

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18 ICH: Blood Pressure Management BP Reduction: preferred IV agents – Labetolol or esmolol (beta blockers) – Nicardipine (CCBs) – Fenoldopam (dopamine agonist) Best to avoid – Nitroprusside Can simultaneously increase ICP lower MAP, and severely decrease CPP Rose J and Mayer SA. Neurocritical Care 2004;1:287.

19 Neurogenic Stress Cardiomyopathy AKA “neurogenic stunned myocardium” Develops within hours of SAH, etc. –Sudden death in 12% of SAH –Post-menopausal females Spectrum of severity Clinical features –Substernal chest pain; dyspnea; cardiogenic shock –CXR with pulmonary edema –Elevated cardiac markers Troponin I peaks on day of rupture BNP

20 Neurogenic Stress Cardiomyopathy –EKG changes 25-75% of patients with SAH Sinus brady or tachy, ST abnormalities, T wave inversions, QTc prolongation Arrhythmias: A-fib, A-flutter, SVT, PVCs, junctional rhythms, ventricular rhythms –Echo Regional wall motion abnormalities beyond single vascular territory Apical ballooning akinesis or dyskinesis Reduced LVEF –Normal coronary angiogram

21 Neurogenic Stress Cardiomyopathy Normal Abnormal

22 Cardiac Echo NormalAbnormal

23 Clinical Signs of Elevated ICP Combination of signs Depressed level of consciousness Reflex hypertension, with or without bradycardia Headache Vomiting Papilledema Cranial nerve palsies

24 Cerebral Herniation Syndromes Decreased cerebral perfusion pressure causing ischemia Midline shift causing ventricular obstruction Types 1.Uncal 2.Central (and # 6) 3.Cingulate (subfalcine) 4.Transcalvarial 5.Cerebellar

25 ICH: Cerebral Edema Dexamethasone – No benefit on outcome, but complications (infections and hyperglycemia) are more common Poungvarin N, et al, N Engl J Med 1987;316:1229 Tellz H, et al, Stroke 1973;4(4):  STANDARD: No Steroids!

26 ICH: Cerebral Edema Osmolar therapy – Glycerol has no effect on outcome –High-dose mannitol (1.4 g/kg) results in better ICP control and early clinical response than lower doses Yu YL, et al, Stroke 1992; 23:967 Cruz J, et al, Neurosurgery 2002; 51:628.  GUIDELINE: Mannitol 20% for patients with increased ICP or symptomatic mass effect  OPTION: 23.4% HTS (30 ml)

27 Intracranial HTN Teatment Modalities Insert ICP monitor General goals: Maintain ICP 65 mm Hg For ICP > mm Hg for > 5 minutes –Drain CSF via ventriculostomy –Elevate head of bed –Osmotherapy –Sedation, agitation and fever control –Hyperventilation –Pressor therapy to maintain MAP and ensure CPP For refractory intracranial HTN –Phenobarbital/Hypothermia/Decompressive craniotomy

28 Osmolality of IV fluids FluidOsmolality (mOsm/kg) 5% Dextrose252 Lactated ringers Plasma285 5% Albumin290 Normal Saline 0.9%308 25% Albumin310 6% Hetastarch310 2% Normal Saline682 3% Normal Saline % Mannitol % Normal Saline 23.4% Normal Saline

29 BWH NeuroICU Protocol for Mannitol Na, BUN, Glu, Cr, Glu and osm 1 hour prior to dosing mannitol Check Na, BUN, Glu, Osm Is Osm > 310 YesNo Calculate Osm GapAdminister mannitol If gap < 10 & Na < 160 Give mannitol If gap > 10 or Na > 160 Hold mannitol and notify HO Osm gap=measured osm- calculated osm Calculated Osm 2(Na)+BUN/2.8+Glu/18

30 Early seizures after ICH Clinically apparent seizures –4% in 1 st 24 hours; 8% in 1 st month –Predictors: lobar location, small ICH volume –No convincing effect on outcome Electrographic seizures –28-31% by continuous EEG over ~ 72 hours –Predictors; hematoma enlargement on 24-hr CT –Periodic discharges associated with poor outcome Passero et al, Epilepsia, 2002 Vespa et al, Neurology, 2003 Classen et al, Neurology, 2007 Kilpatrick et, Arch Neurolgoy 1990 Franke et al, JNNP, 1992

31 ICH: Seizure Prophylaxis Seizure after ICH – 10% have generalized tonic-clonic seizures Passero S, et al, Epilepsia 2002;43:1175. OPTION: Prophylactic anticonvulsants for 7 days for patients with large ICH at risk for increased ICP

32 ICH: Non-Convulsive Seizures Continuous EEG Monitoring – Stuporous or comatose patients with nonconvulsive seizures or SE detected only with cEEG – NCSE is associated with clinical worsening, increased midline shift, and hematoma expansion Vespa P, et al, Neurology 2003;60:1441 Claassen, J et al, Neurology 2007;69:1356  OPTION: Midazolam, Propofol, or Pentobarbital infusion for NCSE

33 –Increased rate of 33%-expansion (54% vs. 16%) –Larger effect than admission SBP, DBP or pulse pressure –Independent effect on mortality and functional outcome Warfarin-related ICH most severe Flibotte JJ. Neurology 2004;63:

34 Coumadin Reversal: FFP Replaces all clotting factors May need 6-8+ U FFP to fully reverse May not reverse all patients Takes time and resources Takes volume ->CHF risk in elderly Has been replaced EU with PCC to reduce volume

35 Coumadin Reversal - PCCs Contains varying amounts of Vitamin K dependent factors (II, VII, IX, X) and particularly VII Lot to lot variability in factor levels Given over minutes May be superior to FFP as a source of factor replacement Recommended in critical/life threatening bleeding associated with warfarin (Ansell, Chest 2004) Difficult to use at most U.S. hospitals –Unfamiliar to most ED personnel –May require hematology consultation

36 Treatment of Warfarin Associated ICH Aguilar et al Mayo Clin Proc. 2007;82:82-92

37 Treatment of Warfarin Associated ICH Aguilar et al Mayo Clin Proc. 2007;82:82-92

38 ICH: Coagulopathy Emergency reversal of warfarin – Prothrombin complex concentrate (PCC) corrects the INR faster than fresh frozen plasma (FFP) – Worsening occurs more often when INR remains >1.4 Freeman WD, et al, Mayo Clin Proc 2004;79:1495 Yasaka M, et al, Thromb Haemostasis 2003;89:278  GUIDELINE: Vitamin K 10 mg IV and FFP (15 ml/kg) or PCC ( U/kg)  OPTION: Recombinant FVIIa

39 Reversal of Treatments Warfarin –Vitamin K –Fresh frozen plasma –Protein complex concentrates Dabigatran – Direct Thrombin Inhibitor –No antidote –Hemodialysis Rivaroxaban/Apixiban – Direct Factor Xa Inhibitor –Hemostatics PCC, rFVIIa may be considered but not been evaluated –NOT dialyzable

40 Surgical Therapies for ICH Surgical evacuation –Large (>3 cm) cerebellar hemorrhages –Large lobular hemorrhages –Substantial mass effect –Rapidly deteriorating condition. O’Connell KA, et al. JAMA. 2006;295:

41 STICH Trial: Surgery for ICH? 1033 enrolled Eligible if clinical equipoise Enrollment within 72 hours of onset –Early surgery –No early surgery No effect on mortality No effect of outcome Early Surgery No Early Surgery Dead or Disabled 63%64% Good Outcome 26%24% Mendelow DA, et al, Lancet 2005;365;387

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44 365-Day MISTIE II MESSAGE Greater benefit at 365 than 180 days 14% upward shift across mRS levels 5 to 0 at 365 days % fewer MIS-treated subjects in LTC facilities Shorter hospital stay for MIS-treated subjects Estimated acute-care cost savings of $44,000

45 ICH: DVT Prophylaxis DVT prophylaxis – Heparin 5000 U SC q12H started on day 2 is safe and reduces DVT/PE – STANDARD: Start low dose subcutaneous heparin on day 2 – OPTION: Enoxaparin 40 mg qd Boeer A, et al, J Neurology Neurosurg Psychiatry 1991;54:466

46 Neurocritical Care Units Can Improve ICH Outcome

47 Summary Epidemiology Imaging Prognosis Neurogenic stress cardiomyopathy Seizures Hypertonic saline Protein complex concentrates New research

48 Thank You Galen V. Henderson, MD


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