Outline Epidemiology Imaging Prognosis Neurogenic stress cardiomyopathy Subclinical seizures Hypertonic saline Protein complex concentrates New treatments
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.
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
Qureshi AI et al. N Engl J Med. 2001;344:1450-1460. 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
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.
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.
ICH Volume Powerful Determinant of 30-day Outcome Condition at 30 days (Oxford Handicap Scale) Broderick JP et al. Stroke. 1993;24:987-993. Good recovery with volume > 30 mL does not occur
28 mL 43 mL Image courtesy T. Brott, MD. Slide No. 12
Goldstein, J. N. et al. Neurology 2007;68:889-894 Contrast within the hematoma
GRE Sequences and Cerebral Amyloid Angiopathy Lobar Hemorrhage Microbleeds
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
Hemphill, J. C. et al. Stroke 2001;32:891-897 The ICH Score and 30-day mortality
Rost, N. S. et al. Stroke 2008;39:2304-2309 FUNC score prediction tool
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.
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
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
Neurogenic Stress Cardiomyopathy Normal Abnormal
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):541-6. STANDARD: No Steroids!
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)
Intracranial HTN Teatment Modalities Insert ICP monitor General goals: Maintain ICP 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
Osmolality of IV fluids FluidOsmolality (mOsm/kg) 5% Dextrose252 Lactated ringers250-260 Plasma285 5% Albumin290 Normal Saline 0.9%308 25% Albumin310 6% Hetastarch310 2% Normal Saline682 3% Normal Saline1025 25% Mannitol1375 7.5% Normal Saline 23.4% Normal Saline 2400 8008
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
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
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
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
–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;63:1059-1064.
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
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
Treatment of Warfarin Associated ICH Aguilar et al Mayo Clin Proc. 2007;82:82-92
Treatment of Warfarin Associated ICH Aguilar et al Mayo Clin Proc. 2007;82:82-92
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 (15- 30 U/kg) OPTION: Recombinant FVIIa
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
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.
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
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
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
Neurocritical Care Units Can Improve ICH Outcome
Summary Epidemiology Imaging Prognosis Neurogenic stress cardiomyopathy Seizures Hypertonic saline Protein complex concentrates New research
Thank You Galen V. Henderson, MD firstname.lastname@example.org