Modern Management of ICH

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Modern Management of ICH Bradley A. Gross, MD Assistant Professor, Dept of Neurosurgery, University of Pittsburgh October 2018

ICH Background Assessment & Diagnosis Medical Management Surgical Management 2/37

Background ICH accounts for 20% of all stroke 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 Aneurysm Venous Sinus Thrombosis 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 > 30 Drinks Per Month or Binge Drinker Non-HDL Cholesterol (Third vs First Tertile) HDL Cholesterol (Third vs First Tertile) 1.52 (99% CI 1.07-2.16) 2.01 (99% CI 1.35-2.99) 0.50 (99% CI 0.34-0.72) 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

22% Deteriorate in Transport Crit Care Med 2008; 36: 172-175 Presentation 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, Anticoagulant), Exam Ischemic/Hemorrhagic Stroke Acute Onset Focal Deficit HTN / Blood Pressure Lability Hemorrhagic Stroke Headache Nausea/Vomiting Depressed Mental Status

Diagnosis Rapid Imaging (Class I, Level A) Advanced Imaging For Underlying Lesion (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 basal ganglia / cerebellar bleed > negative CTA MRI DSA

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 intracerebral hemorrhage. 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 Seizure (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 Hematoma Growth, Improve Outcome

What s the Deal with Blood Pressure?

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)

Coagulopathy 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%.

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 Hydrocephalus 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 Brainstem 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)

18-80 yo with spontaneous 20 cc + bleed MIS: Image Guided Placement of Catheter, Aspiration, rtpa rtpa 0.3 mg to 1.0 mg q8h up to 9 doses 54 MIS plus rtpa vs 42 Medical Care 30 day mortality: 9.5% vs 14.8% (p = 0.54) 7 day mortality: 0% vs 1.9% (p = 0.56) Symptomatic Bleed: 2.4% vs 9.3% (p = 0.23) Infection: 2.4% vs 0% (p = 0.43) Asymptomatic Bleed: 22.2% vs 7.1% (p = 0.051) MISTIE III: 180 day functional outcome comparison

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

Acknowledgments