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Cerebral Hemorrhage

Cerebral Hemorrhage. Galen V. Henderson, M.D. Brigham and Women ’ s Hospital Director, Neuroscience ICU Harvard Medical School. Disclosures. I have no industry relationships. Outline. Epidemiology Imaging Prognosis Neurogenic stress cardiomyopathy Subclinical seizures

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Cerebral Hemorrhage

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  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;344:1450-1460. Broderick JP et al. Stroke. 1999;30:905-915; Broderick JP et al. N Engl J Med. 1992;326:733-736. 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. Most Common Sites of ICH Cerebral lobes 50% deep 35% lobar 10% cerebellum 6% brainstem Thalamus Basal ganglia Cerebellum Pons Qureshi AI et al. N Engl J Med. 2001;344:1450-1460. Broderick JP, et al. Stroke. 2007;38:1-23.

  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. Good recovery with volume > 30 mL does not occur ICH Volume Powerful Determinant of 30-day Outcome Condition at 30 days (Oxford Handicap Scale) Broderick JP et al. Stroke. 1993;24:987-993.

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

  12. Contrast within the hematoma Goldstein, J. N. et al. Neurology 2007;68:889-894

  13. GRE Sequences and Cerebral Amyloid Angiopathy Microbleeds Lobar Hemorrhage

  14. The ICH Score Components

  15. The ICH Score and 30-day mortality Hemphill, J. C. et al. Stroke 2001;32:891-897

  16. FUNC score prediction tool Rost, N. S. et al. Stroke 2008;39:2304-2309

  17. 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.

  18. 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

  19. 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

  20. Neurogenic Stress Cardiomyopathy Normal Abnormal

  21. Cardiac Echo Normal Abnormal

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

  23. Cerebral Herniation Syndromes • Decreased cerebral perfusion pressure causing ischemia • Midline shift causing ventricular obstruction • Types • Uncal • Central (and # 6) • Cingulate (subfalcine) • Transcalvarial • Cerebellar

  24. ICH: Cerebral Edema • Dexamethasone • No benefit on outcome, but complications (infections and hyperglycemia) are more common • STANDARD: No Steroids! Poungvarin N, et al, N Engl J Med 1987;316:1229 Tellz H, et al, Stroke 1973;4(4):541-6.

  25. 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 • GUIDELINE: Mannitol 20% for patients with increased ICP or symptomatic mass effect • OPTION: 23.4% HTS (30 ml) Yu YL, et al, Stroke 1992; 23:967 Cruz J, et al, Neurosurgery 2002; 51:628.

  26. Intracranial HTN Teatment Modalities • Insert ICP monitor • General goals: Maintain ICP < 20 mm Hg and CPP > 65 mm Hg • For ICP > 20-25 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

  27. Osmolality of IV fluids

  28. BWH NeuroICUProtocol for Mannitol Administer mannitol Calculate Osm Gap Yes No Na, BUN, Glu, Cr, Glu and osm 1 hour prior to dosing mannitol Check Na, BUN, Glu, Osm Is Osm > 310 If gap > 10 or Na > 160 Hold mannitol and notify HO If gap < 10 & Na < 160 Give mannitol • Osm gap=measured osm-calculated osm • Calculated Osm 2(Na)+BUN/2.8+Glu/18

  29. Early seizures after ICH • Clinically apparent seizures • 4% in 1st 24 hours; 8% in 1st 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

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

  31. 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 • OPTION: Midazolam, Propofol, or Pentobarbital infusion for NCSE Vespa P, et al, Neurology 2003;60:1441 Claassen, J et al, Neurology 2007;69:1356

  32. Warfarin-related ICH most severe • Increased rate of 33%-expansion (54% vs. 16%) • Larger effect than admission SBP, DBP or pulse pressure • Independent effect on mortality and functional outcome Flibotte JJ. Neurology 2004;63:1059-1064.

  33. 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

  34. 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 10-15 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

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

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

  37. 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 • GUIDELINE: Vitamin K 10 mg IV and FFP (15 ml/kg) or PCC (15-30 U/kg) • OPTION: Recombinant FVIIa Freeman WD, et al, Mayo Clin Proc 2004;79:1495 Yasaka M, et al, Thromb Haemostasis 2003;89:278

  38. 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

  39. 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;295:293-298.

  40. 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 Mendelow DA, et al, Lancet 2005;365;387

  41. 365-Day MISTIE II MESSAGE • Greater benefit at 365 than 180 days • 14% upward shift across mRS levels 5 to 0 at 365 days • 13 -14% fewer MIS-treated subjects in LTC facilities • Shorter hospital stay for MIS-treated subjects • Estimated acute-care cost savings of $44,000

  42. 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

  43. Neurocritical Care Units Can Improve ICH Outcome

  44. Summary • Epidemiology • Imaging • Prognosis • Neurogenic stress cardiomyopathy • Seizures • Hypertonic saline • Protein complex concentrates • New research

  45. Thank You Galen V. Henderson, MD ghenderson@partners.org

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