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Home , Intracerebral hemorrhage

Evidence-Based Management of Intraparenchymal Hemorrhage

Bradley A. Gross, MD Assistant Professor, Dept of , University of Pittsburgh October 2019 ICH

• Background • Assessment & Diagnosis • Medical Management • Surgical Management Background

• ICH accounts for 20% of all • Most common form of hemorrhagic stroke • Meta Analysis of 36 Studies • Incidence of 24.6/100,000 person-years • No Sex Predilection • Incidence Increases With Age • Median 1 Month Fatality 40.4% (13.1-60%) • Primary IPH • HTN • CAA • Secondary IPH • AVM • dAVF • Cav Mal • Mycotic • Venous Sinus • Moyamoya • Vasculitis • Hemorrhagic Tumor • Hemorrhagic Ischemic Stroke • Case-Control Study in 22 Countries • 3000 Cases (663 ICH) with 3000 controls

Risk Factor OR of ICH

Self-reported history of HTN or SBP > 160/90 9.18 (99% CI 6.80-12.39)

Current Smoker 1.45 (99% CI 1.07-1.96)

1-30 Drinks Per Month 1.52 (99% CI 1.07-2.16) > 30 Drinks Per Month or Binge Drinker 2.01 (99% CI 1.35-2.99) Non-HDL (Third vs First Tertile) 0.50 (99% CI 0.34-0.72) HDL Cholesterol (Third vs First Tertile) 1.91 (99% CI 1.29-2.83)

110 patients all undergoing autopsy with ICH ICH

• Background • Assessment & Diagnosis • Medical Management • Surgical Management

9/37 Presentation

• 22% Deteriorate in Transport • Crit Care Med 2008; 36: 172-175 • 23% GCS 13-15 in ED deteriorate at least 2 points in ED • Predictors: Antiplatelet use, ictus to ED arrival < 3 hours, Temp at least 37.5C, IVH, 2 mm or more MLS • Acad Emerg Med 2012; 19: 133-138

• ED Evaluation: Time of Onset, PMH (HTN, ), Exam • Ischemic/Hemorrhagic Stroke • Hemorrhagic Stroke • Acute Onset • • Focal Deficit • Nausea/ • HTN / Lability • Depressed Mental Status

Diagnosis

• Rapid Imaging (Class I, Level A) • Advanced Imaging For Underlying (Class IIa, Level B) • CTA • Positive Predictors (JNS 2012; 117: 761-766): • Age < 65 (OR 16.36) • Female Sex (OR 14.9) • Nonsmoker (OR 103.8) • IVH Presence (OR 9.42) • No HTN (OR 515.78) • HTN, older than 65 with / cerebellar bleed > negative CTA • MRI • DSA All patients within 6 hours of symptom onset • 63yo F HTN, HL, DM, smoker Assessment

• Baseline Severity Score Should Be Performed – Class I, Level of Evidence B

ICH Score Factors Mortality GCS Score (3-4, 2 points; 5-12, 1 point) 0 points = 0% Age at least 80 (1 point) 1 point = 13% Infratentorial Hemorrhage Origin (1 point) 2 points = 26% Volume of at least 30 cc (1 point) 3 points = 72% Intraventricular Blood (1 point) 4 points = 97% 5 points = 100%

Hemphill JC, et al. The ICH Score: a simple, reliable grading scale for . Stroke 2001; 32: 891-897. ICH

• Background • Assessment & Diagnosis • Medical Management • Surgical Management

15/37 Initial / Medical Management

• Secure Airway As Indicated • Avoid Hyper/Hypoglycemia (Class I, Level C) • AED if (Class I, Level A) • Screening EKG and Tn (Class IIa, Level C) • BP Control (< 140) • Coagulopathy Management • ICU / Stroke Unit Admission (Class I, Level B) • No: Prophylactic AED, rVIIa, Tranexamic Acid, Steroids

• GOAL: Mitigate Growth, Improve Outcome 817 patients with IPH Hematoma Expansion in 19% (6 cc or by 33%)

No Impact On Hematoma Growth: Age, Sex Antiplatelet Usage Presenting GCS Amyloid ICH Location Presence of IVH • INTEnsive blood pressure Reduction in Acute Cerebral Hemorrhage (INTERACT2) • INTERACT-1 RCT in Lancet Neurol 2008 of 500 patients with less hematoma growth with SBP < 140 • Spontaneous “nonmassive” ICH, GCS 6+ • 1382 Patients SBP 110-139 vs 1412 Patients SBP 140-179 • Initiated within 6 hours after bleed for next 7 days • mRS 3-6 in 52.0% vs 55.6% at 3 months (p = 0.06); meets significance in ordinal analysis • Serious Adverse Events 23.3% vs 23.6%. • Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) • ATACH – feasibility and safety of three BP tiers in 60 patients (Crit Care Med 2010) • Spontaneous Supratentorial ICH < 60 cc, GCS 5+ • 500 Patients SBP 110-139 vs 500 Patients SBP 140-179 via cardene gtt • Initiated within 4.5 hours after symptom onset for next 24 hours with SBP > 180 • mRS 4-6 in 38.7% vs 37.7% at 3 months • Overall Treatment-Related Serious Adverse Events 1.6% vs 1.2% • Hematoma Expansion (33% or more at 24 hours) 18.9% vs 24.4% (p = 0.08) • Renal Adverse Events 9% vs 4% (p = 0.002) • Mean SBP 128.9 vs 141.1 in two hours (150 vs 164 in INTERACT2) • Achieved systolic blood pressure was continuously associated with functional outcome. Management

• Repletion for Coagulation Factor Deficiency/Thrombocytopenia (Class I Level C) • Reversal of Anticoagulation • If VKA: PCC (Class IIb Level B), Vit K (Class I Level C) • Hematoma growth: 19% if PCC vs 33% FFP • FFP = fluid overload, similar thromboembolic complications • Protamine Sulfate for Heparin (Class IIb Level C) • ? Reversal of Antiplatelet • Spontaneous supratentorial ICH within 6 hrs of Sx • Used antiplatelet for at least 7 days prior • 78% Cox-I, 16% Cox-I + Dipyridamole, 3% ADP-I, 2% Cox-I + ADP-I • GCS at least 8 • 97 transfusion vs 93 standard care • Alive at 3 months 68% vs 77% (OR 0.62, 95% CI 0.33-1.19) • mRS 4-6 at 3 months 72% vs 56% (OR 2.04, 95% CI 1.12-3.74) • mRS 3-6 at 3 months 78% vs 82% (OR 1.75, 95% CI 0.77-3.97) • Median ICH growth at 24 hours 2.01 vs 1.16 (p = 0.81) • Serious adverse event: 42% vs 29%. 537 adults taking antiplatelet/anticoagulant with ICH Randomized to restarting antiplatelet in 24 hrs at least 24 hrs post ictus Recurrent Symptomatic ICH: 4% vs 9% (p = 0.06) Major Hemorrhagic Events: 7% vs 9% (p = 0.27) Major Occlusive Vascular Events: 15% vs 14% (p = 0.92)

Recurrent Symptomatic ICH / Stroke: 4% vs 9% (p = 0.04) ICU / Stroke Unit Admission (Class I, Level B)

• Greater chance of independence! • Terent et al. JNNP 2009: • 8206 patients in stroke unit vs 2871 on standard ward • 3 month death / dependence 59% vs 75% • (OR 0.59, 95% CI 0.53-0.67)

Early dysphagia screen (Class I, Level B) Intermittent Pneumatic Compression (Class I, Level A) CLOTS (Clots in Legs Or sTockings after Stroke), Lancet 2013; 382: 516-524: DVT rate: 8.5% vs 12.1% (p < 0.05) SC Heparin / LMWH 1-4 days after stability (Class IIb, Level B) • UFH/LMWH within 24-96 hr • DVT rate: 3.3% vs 4.2%, (RR 0.77, 95% CI 0.44-1.34) • PE rate: 1.7% vs 2.9% (RR 0.37, 95% CI 0.17-0.80) • Hematoma Enlargement rate: 8.0% vs 4.0% (RR 1.42, 95% CI 0.57-3.53) • Mortality 16.1% vs. 20.9% (RR 0.76, 95% CI 0.57-1.03) ICH

• Background • Assessment & Diagnosis • Medical Management • Surgical Management

24/37 Neurosurgical Consultation

• • 23% of all patients in STICH, 55% if IVH • EVD • “Decreased LOC” (Class IIa Level B) • GCS < 9 (Class IIb, Level C) • Surgical Evacuation • > 3 cm Cerebellar IPH (Class I, Level B) • Deteriorating • Compression/Hydrocephalus • Supratentorial IPH • Large Hematoma with shift (Class IIB, Level C) 6 mo mRS 2 • 1003 patients from 83 centres in 27 countries • Minimum hematoma diameter of 2 cm, GCS at least 5 • Early surgery (n = 503) or conservative treatment (n = 530) • 6 month Favourable Outcome: 26% vs 24% • GOS good recovery / moderate disability • (OR 0.89, 95% CI 0.66-1.19) • 601 patients from78 centres in 27 countries • Superficial Hematoma 10 -100 cc (1 cm from surface), GCS 8+ • Early surgery (n = 307) or conservative treatment (n = 294) • 6 month Unfavourable Outcome: 59% vs 62% (p = 0.37)

• Spontaneous 30 cc + bleed • MIS: Image Guided Placement of , Aspiration, rtPA • rtPA 1.0 mg q8h up to 9 doses • 250 MIS plus rtPA vs 249 Medical Care • mRS 0-3 at 1 yr: 45% vs 41% (p = 0.33) • 39 cases • Median GCS 10, 36 cc hematoma volume • 52% mRS 2 or less, no mortality ENRICH

• Early miNimally invasive Removal of IntraCerebral Hemorrhage • Age 18-80, GCS 5-14, 30-80 cc IPH • Brainpath vs medical management within 24 hours • Primary outcome utility-weighted mRS at 180 days Secondary ICH

Etiology Dx Tx

AVM CTA / DSA Surgery / SRS / Embolization dAVF CTA / DSA Embolization / Surgery

Cavernous Malformation MRI Surgery

Distal/Mycotic Aneurysm CTA / DSA Embolization/ Surgery

Venous Sinus Thrombosis CTV Thrombectomy/Anticoagulation

Moyamoya CTA / DSA Revascularization

Vasculitis CTA / DSA Rx

Tumor MRI / Surgery Surgery / SRS Summary

• ICH accounts for 20% of all Stroke • Median 1 month fatality 40% • ICH Risk Factors: HTN, Smoking, EtOH, HDL Cholesterol • CAA recurrent ICH rate: 7.4% / yr vs 1.1% / yr • CAA Factors: SAH, Finger projections, Apoe4 • Hemphill Score: GCS, Age > 80, Infratentorial, IVH, > 30 cc • SBP < 140, Coagulopathy Management, ICU Admission • EVD for hydrocephalus, Evacuate/Decompress if Cerebellar > 3 cm / Herniation • Minimally Invasive Trials for Supratentorial Bleeds